Resveratrol, an effective regulator of ovarian development and oocyte apoptosis.

Resveratrol, a phytopolyphenol compound found chiefly in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. However, little is known about the effects of resveratrol on ovarian development and oocyte apoptosis. We investigated the effects of resveratrol on ovarian development in rats with different ages [from post-natal day (PD) 1 to 15 months], as well as on oocyte apoptosis in PD1 and PD2 rat ovaries. We show that: a) ip injection of resveratrol (20 mg/kg/day) increased the percentage of unassembled follicles and the total number of oocytes in PD1 and PD2 rat ovaries. Similar results were obtained when mothers were treated with resveratrol (20 mg/kg/day) by intragastric administration from day 11, after the detection of vaginal plug, until delivery. In PD4 rat ovaries, the total number of oocytes was significantly increased in the groups treated with resveratrol. Moreover, more unassembled follicles and fewer primary follicles were present in the groups treated with resveratrol than in the controls; b) in 15-month-old rat ovaries, resveratrol increased the number of resting follicles and total oocytes, and decreased the number of developing follicles and atretic follicles; 3) the percentage of TUNEL-positive oocytes decreased in PD1 and PD2 rat ovaries after resveratrol treatment, and the number of oocytes positive for Foxo3a, Bim, and p27KIP1 in PD2 rat ovaries was lower in the resveratrol treatment group than in controls. These results suggest that resveratrol may delay oocyte nest breakdown and inhibit both the primordial-to-developing-follicle transition and apoptosis by decreasing the activation of Foxo3a, Bim, and p27KIP1, thus augmenting the resting follicle reserves, maintaining regular estrous cycles of early aged rats and delaying climacterium.

Performance of the rapidly extracted auditory evoked potentials index to detect the recovery and loss of wakefulness in anesthetized and paralyzed patients.

BACKGROUND: The rapidly extracted auditory evoked potentials index (A-lineTM ARX Index or AAI) has been proposed as a method to measure the depth of anesthesia. A prospective study was designed to assess the performance of AAI to detect the recovery and loss of wakefulness in anesthetized and paralyzed patients. METHODS: Fourteen adult patients undergoing elective surgery were anesthetized with propofol 1.5 mg kg-1, vecuronium 0.1 mg kg-1 and further propofol 1.0 mg kg-1. Wakefulness was measured by the ability of the patient to respond to command using the isolated forearm technique (IFT). After the patient responded, propofol was infused at 10 mg kg-1. h-1 until wakefulness (responsiveness) was lost. The AAI was recorded continuously throughout the study and analyzed off-line. RESULTS: The AAI showed a significant difference between the values registered during, 30 s before and 30 s after the recovery, and also between 30 s before and 30 s after the loss of wakefulness. The prediction probability (Pk) values for AAI were 0.786 and 0.864 during the transitions from unresponsiveness to responsiveness and from responsiveness to unresponsiveness. The area under the receiver operating characteristic curve for the responsive and unresponsive values was 0.926 (SE 0.002, 95% CI 0.922-0.931), and the AAI values of approximately 5%, 50% and 95% predicted probability of wakefulness were 19, 29 and 39, respectively. CONCLUSION: The AAI may be a good predictor of recovery and loss of wakefulness for anesthetized and paralyzed patients.

Changes in the rapidly extracted auditory evoked potentials index and the bispectral index during sedation induced by propofol or midazolam under epidural block.

BACKGROUND: The bispectral index (BIS) and the rapidly extracted auditory evoked potentials index (A-line ARX Index or AAI) have been proposed as methods to measure the depth of sedation. A prospective study was designed to assess the performance of both these methods for measuring the depth of sedation induced by propofol or midazolam under epidural block. METHODS: Thirty-two ASA I and II adult patients undergoing elective gynaecological surgery under low-thoracolumbar epidural block were studied. Eighteen patients received propofol (Group P: 20 mg bolus every 3 min) and 14 received midazolam (Group M: 0.5 mg bolus every 5 min) until an observer's assessment of alertness/sedation (OAA/S) scale score of 1 was achieved. AAI and BIS were monitored for different OAA/S scores. RESULTS: AAI and BIS decreased and increased following the changes on the patients' OAA/S scores and correlated with sedation significantly. During the onset phase, the coefficients of Spearman's rank correlation for AAI and BIS were respectively 0.958 and 0.898 (P < 0.001) for Group P, and 0.973 and 0.945 (P < 0.001) for Group M. During the recovery phase in Group P, the coefficients were respectively 0.946 and 0.702 (P < 0.001). Linear regression analysis showed that both AAI and BIS were linearly related to the OAA/S scores. The coefficients of Spearman's rank correlation and linear regression for AAI were all greater than those for BIS (P < 0.05). CONCLUSIONS: Both AAI and BIS correlated well with the depth of sedation induced by propofol or midazolam under epidural block. AAI may be more valuable when monitoring depth of sedation.

Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents of the dorsal horn neurons in newborn rats.

BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons. METHODS: Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations. CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).

Preparation of levoglucosan by pyrolysis of cellulose and its citric acid fermentation.

Levoglucosan (LG), 1,6-anhydro-beta-D-glucopyranose, was produced by pyrolysis of cellulose. A response surface method was used to optimize the reaction parameters: X1, temperature; X2, time required for heating cellulose from room temperature to the designed pyrolysis temperature; and X3, vacuum, and a Box-Behnken design was employed for this purpose. The optimal temperature and time were found to be 388 degrees C and 26.2 min by fixing the vacuum at 1 mm Hg. The levoglucosan prepared was fermented to citric acid by Aspergillus niger CBX-209, which was a mutant derived by gamma-ray mutagenesis of the parent strain CBX-2. The mutant could produce increasing citric acid with increasing LG purity and had a citric acid yield of 87.5% when using purified levoglucosan as the sole carbon source in a 5 day fermentation period.

The effects of ropivacaine on sodium currents in dorsal horn neurons of neonatal rats.

We used a whole cell patch clamp technique to study the effects of ropivacaine on rat dorsal horn neurons. Under voltage clamp, ropivacaine (10-400 microM) produced a dose-dependent inhibition of sodium current. From a holding potential (V(h)) of -80 mV, sodium currents evoked by test pulses to 0 mV were inhibited by ropivacaine with a mean drug concentration required to produce 50% current inhibition (IC(50)) value of 117.3 microM, which was more than the value of the bupivacaine (IC(50) 53.7 microM). The inhibition effect of ropivacaine was also voltage-dependent. Current evoked from a V(h) of -60 mV was inhibited by ropivacaine with a mean IC(50) value of 74.3 microM, which was less than that obtained at the V(h) of -80 mV. The inhibition effect of ropivacaine on sodium current was use dependent. Repeated activation by a train of depolarizing pulses (5 Hz, 20 ms) increased the inhibitory effects of ropivacaine. The ratio amplitudes of the 20th to the first pulse were 91.2% and 71.1%, respectively, in the absence and presence of ropivacaine (50 microM). Ropivacaine also produced a significant hyperpolarizing shift of 11 mV in the steady-state inactivation curve of sodium current. The inhibition of ropivacaine on the sodium channel may contribute to the mechanism of action of local anesthetics during epidural and spinal anesthesia.

[Hemodynamic changes in normovolemic and hypovolemic canines during epidural block].

Hemodynamic changes were studied in normovolemic and hypovolemic canines during epidural block. In normovolemic canines after epidural block, stroke volume (SV) increased, heart rate (HR) slowed down and total peripheral resistance (TPR) and mean arterial pressure (MAP) decreased. In addition, hepatic vascular resistance (HVR) and renal vascular resistance (RVR) decreased but quantity of hepatic artery per beat (QHR/HR), quantity of hepatic artery per beat (QPV/HR) and quantity of renal artery per beat (QRA/HR) increased significantly. In hypovolemic canines, the hemodynamic changes after epidural block were similar in normovolemic ones but more abrupt. The increase of QHA/HR, QPV/HR and QRA/HR was not statistically significant, but minute hepatic blood volume quantity of hepatic artery (QHA), quantity of portal vein (QPV) and hepatic blood flow (HBF) decreased significantly. In hypovolemic canines during epidural block, ischemic injury of the liver should be alerted and abrupt hemodynamic changes should be well controlled.

[Synthesis and radiosensitizing activity of benzimidazoles].

In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl-oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3'-pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively.