Curative effect and costs of surgical and gamma knife treatments on intractable epilepsy caused by temporal-hippocampal sclerosis.

This study aimed to investigate the curative effect and costs of surgical and gamma knife treatments on intractable epilepsy caused by temporal-hippocampal sclerosis. The subjects comprised patients who suffered from intractable epilepsy caused by temporal-hippocampal sclerosis and received treatment in the Department of Neurosurgery of our hospital between 2010 and 2011. After obtaining their consent, patients were evaluated and selected to receive surgical or gamma knife treatments. In the surgical group, the short-term curative rate was 92.60% and the average cost was US$ 1311.50 while in the gamma knife group, the short-term curative rate was 53.79%, and the average cost was US$ 2786.90. Both surgical and gamma knife treatments of intractable epilepsy caused by temporal-hippocampal sclerosis are safe and effective, but the short-term curative effect of surgical treatment is better than that of gamma knife, and its cost is lower.

[Effects of free radicals and amyloid beta protein on the currents of expressed rat receptors in Xenopus oocytes].

AIM: To investigate the effects of free radicals (FRs) and amyloid beta protein (A beta 1-40) on the functions of expressed neurotransmitter receptors (NRs) from rat brains in Xenopus oocytes. METHODS: Total RNA and Messenger RNA (mRNA) was prepared from 3-month-old Wistar rat brain tissues with Promega kits and microinjected into mature Xenopus oocytes (stage V - VI) with 50 nl (50 ng) for each oocyte for receptor expression and their currents were recorded with double electrode voltage clamp technique. Superoxide anion free radicals (SAFRs) and A beta 1-40 was added 12 h, 24 h, 96 h to incubation solution before recording. RESULTS: The results showed that oocytes expressed mACh, glutamate, dopamine, serotonin and gamma-aminobutyric acid receptors. The current characteristics of these receptors were inward currents carried by chloride ion with their equilibrium potentials close to - 22 mV. A beta 1-40 and free radicals had a kind of inhibitory effect on the expressed GluR. When treated with 60 nmol/L A beta 1-40 over 24 h, the currents of GluR significantly decreased (25% off, P < :0.01). When oocytes were co-treated with 60 nmol/L A beta 1-40 and SAFRs over a period of 12 h, the currents of glutamate receptor significantly decreased (21% of P < 0.05), and the decreased percentage reached 52% over 24h co-treated with 60 nmol/L A beta 1-40 and SAFRs. Vitamin E had partial antagonistic effect against these effects. CONCLUSION: The result suggests that A beta has a kind of inhibitory effects upon glutamate receptor, which is similar to those of free radicals. Their effects can be antagonized by vitamin E. This implies that A beta may play roles via inhibiting receptor function in pathophysiology of Alzheimer's disease.

Synergistic effects of clinically achievable concentrations of 12-O-tetradecanoylphorbol-13-acetate in combination with all-trans retinoic acid, 1alpha,25-dihydroxyvitamin D3, and sodium butyrate on differentiation in HL-60 cells.

Our recent studies demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) has pharmacological activity for the treatment of acute myelocytic leukemia patients. In the present study, we investigated the potential synergistic effect of all-trans retinoic acid (RA), 1alpha,25-dihydroxyvitamin D3 (VD3), and sodium butyrate (NaB) on TPA-induced differentiation in HL-60 human promyelocytic leukemia cells. The cells were treated once with these agents for 48 h or treated every 24 h for 96 h. Treatment of HL-60 cells once with TPA, RA, VD3, or NaB for 48 h resulted in concentration-dependent growth inhibition and cell differentiation. At clinically achievable concentrations, TPA (0.16 nM) increased the number of adherent cells and RA (0.1-1 microM) increased the number of nitroblue tetrazolium (NBT)-positive cells. The combinations of TPA (0.16 nM) with RA (0.1-1 microM), VD3 (1 nM), or NaB (100 microM) for 48 h synergistically increased differentiation as measured by the formation of adherent cells (P < or = 0.01). Moreover, cells treated with various combinations of low concentrations of TPA, RA, VD3, and NaB every 24 h for 96 h resulted in a further decrease in cell growth and an increase in differentiation. At clinically achievable concentrations, the strongest stimulation of differentiation was achieved in cells treated with a "cocktail" that combined TPA, RA, VD3, and NaB. The synergistic effect of combinations of TPA with RA or NaB at clinically effective concentrations on HL-60 cell differentiation suggests that the combination of these agents may improve the therapeutic efficacy of TPA for the treatment of acute promyelocytic leukemia (APL) patients. A differentiation "cocktail" that combines TPA, RA, VD3, and NaB may provide an even more effective strategy for improving the therapeutic efficacy of TPA and RA.

Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with myelocytic leukemia: preliminary studies on therapeutic efficacy and toxicity.

Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was shown to have pharmacological activity for the treatment of myelocytic leukemia in patients refractory to cytosine arabinoside (Ara C), retinoic acid, and other antileukemic drugs. Marked decreases in bone marrow myeloblasts as well as temporary remission of disease symptoms were observed when TPA was administered alone or in combination with vitamin D3 and Ara C. Additional studies with TPA after the determination of optimum dosing regimens are needed to determine whether long-lasting or permanent remissions of myelocytic leukemia can be achieved. Transient and reversible side effects were observed after a 1-mg i.v. dose of TPA, but these adverse effects became less intense or disappeared when a lower dose of TPA was used. The results of this study indicate a therapeutic effect of TPA in patients with myelocytic leukemia.

12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced increase in depressed white blood cell counts in patients treated with cytotoxic cancer chemotherapeutic drugs.

Fifty-two patients with solid tumors had depressed white blood cell and neutrophil counts because of prior treatment with cytotoxic cancer chemotherapeutic drugs. These patients were given one or more i.v. infusions of 0.125-0.25 mg of 12-O-tetradecanoylphorbol-13-acetate (TPA), and this treatment increased the low white blood cell and neutrophil counts toward the normal range. The average white blood cell and neutrophil counts were 2.55 x 10(9)/liter and 1.76 x 10(9)/liter, respectively, before treatment with TPA. After one or more i.v. infusions of TPA, the white blood cell and neutrophil counts increased to peak values of 5. 92 x 10(9)/liter and 4.76 x 10(9)/liter, respectively, within a few days. Most patients had increased levels of white blood cells and neutrophils by 24 hr after a single i.v. infusion of 0.25 mg TPA. Elevated levels were observed for at least 3 days. This study demonstrates that treatment with parenteral TPA is feasible with useful biological activity. Only mild and reversible side effects were observed.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of ornithine decarboxylase activity, DNA synthesis, and tumor promotion in mouse skin by ascorbic acid and ascorbyl palmitate.

The effects of topically applied 12-O-tetradecanoylphorbol-13-acetate (TPA) on the level of ascorbic acid in the epidermis and the effects of topically applied ascorbic acid, ascorbyl palmitate (a synthetic lipophilic derivative of ascorbic acid), palmitic acid and sorbitan monopalmitate on TPA-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 5 or 16 nmol of TPA resulted in a 45-50% decrease in the amount of ascorbic acid per mg protein in mouse epidermis at 5 h after TPA application. Large topical doses of ascorbic acid inhibited TPA-induced tumor promotion in mouse epidermis, but smaller doses were inactive. The topical application of relatively small doses of ascorbyl palmitate had a marked inhibitory effect on TPA-induced ornithine decarboxylase activity, DNA synthesis, and tumor promotion in mouse epidermis. Ascorbic acid, palmitic acid, and sorbitan monopalmitate were less effective than ascorbyl palmitate as inhibitors of tumor promotion. The topical application of 4 mumol of ascorbyl palmitate inhibited by 60-76% the induction of epidermal ornithine decarboxylase activity and DNA synthesis that occurred after a single topical application of 2 nmol of TPA whereas similar doses of ascorbic acid had no inhibitory effect. The topical application of 4 mumol of ascorbyl palmitate together with 5 nmol of TPA twice weekly for 20 weeks to previously initiated mice inhibited by 91% the number of tumors per mouse.