Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.

Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family.

The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and the results suggest that the "startle center" is located subcortically.

Probing the importance of the amino-terminal sequence of the beta- and gamma-chains to the properties of normal adult and fetal hemoglobins.

A recombinant mutant of human fetal hemoglobin (Hb F), named rHb Oscar, has been constructed to explore the importance of the sequence of the amino-terminal region of the gamma-chain to the structural and functional properties of Hb F as compared to human normal adult hemoglobin (Hb A). Substitutions in the N-terminal region of Hb A have shown this region to be important to its structural and functional properties. Recent studies of recombinant mutants of Hb A with gamma-chain mutations have been used to probe the significance of the N-terminal sequence to the properties of Hb F. One of these mutants of Hb A, called rHb Felix, contains eight substitutions in the N-terminal region of the beta-chain corresponding to the sequence of the gamma-chain in that region [Dumoulin et al. (1998) J. Biol. Chem. 273, 35032-35038]. rHb Felix exhibits a 2,3-bisphosphoglycerate (2,3-BPG) response like that of Hb A, but its tetramer-dimer dissociation constant is similar to that of Hb F. In contrast, rHb Oscar contains a gamma-chain with eight mutations at the N-terminal end corresponding to the sequence of the beta-chain of Hb A in that region. (1)H NMR studies of rHb Oscar indicate a global structure like that of Hb F. rHb Oscar is not as stable against alkaline denaturation as Hb F but is more stable than Hb A, and it exhibits a stronger response to 2,3-BPG and inositol hexaphosphate as compared to Hb F. The 2,3-BPG effect in rHb Oscar also appears to be slightly enhanced compared to that in Hb A. Subzero isoelectric focusing experiments suggest that rHb Oscar does not have dissociation properties like those of Hb A. These results along with those of rHb Felix illustrate that the effects of the N-terminal region on structure and function of the Hb molecule are complicated by interactions with the rest of the molecule that are not yet well defined. However, studies of complementary mutations of Hb A and Hb F may eventually help to define such interactions and lead to a better understanding of the relationship between the amino acid sequence and the properties of the Hb molecule.

Treatment of spinal muscular atrophy by sodium butyrate.

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increases the amount of exon 7-containing SMN protein in SMA lymphoid cell lines by changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expression of SMN protein in motor neurons of the spinal cord and resulted in significant improvement of SMA clinical symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treatment of human SMA patients.

Effects of paeoniflorin on the formalin-induced nociceptive behaviour in mice.

In this study, we attempted to identify the mechanisms of paeoniflorin on antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.) showed dose-related antinociception both on the early and late phases of formalin test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test. However, the antinociceptive effects of paeoniflorin were not potentiated by L-arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10 microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block the paeoniflorin-induced antinociception on the early phase of formalin test. These results suggested that the central antinociceptive effects of paeoniflorin on formalin test in mice were mediated by the activation of kappa-opioid receptor and not related to the increase of intracellular calcium.

Reversal caused by n-butylidenephthalide from the deficits of inhibitory avoidance performance in rats.

The present study was designed to investigate the mechanism of action of n-butylidenephthalide on the deficits of inhibitory avoidance performance induced by drugs in rats with piracetam as a positive control. n-Butylidenephthalide attenuated the scopolamine-induced and mecamylamine-induced acquisition impairment, and also attenuated the acquisition impairment induced by scopolamine plus mecamylamine. Furthermore, scopolamine methylbromide, a peripheral cholinergic muscarinic receptor antagonist, did not block the counteracting effect of n-butylidenephthalide on the scopolamine-induced acquisition impairment. n-Butylidenephthalide attenuated the impairment of inhibitory avoidance performance induced by the central acetylcholinergic neurotoxin AF64A administered intracisternally. From the above results, we suggest that n-butylidenephthalide attenuated the deficits of inhibitory avoidance performance induced by drugs, which are the effects related to activating the central but not the peripheral cholinergic neuronal system via muscarinic and nicotinic receptors.

Autoantibody against oxidized low-density lipoproteins may be enhanced by cigarette smoking.

A total of 59 healthy male subjects (32 smokers and 27 nonsmokers) who had no reported systemic disease and did not take alcohol and vitamin supplementation were included. The levels of autoantibody to oxidized low-density lipoproteins (ox-LDL) in smokers and age-matched nonsmokers were compared. The plasma levels of antioxidants that can affect the formation of ox-LDL were also measured, and correlation analyses between anti ox-LDL IgG and plasma antioxidants, controlling for age and body mass index (BMI), were performed. Plasma alpha-tocopherol and uric acid concentrations of nonsmokers (2.78+/-1.09 microg/mg total lipid and 6.96+/-1.69 mg/dl, respectively) were significantly higher than those of smokers (1.68+/-0.48 microg/mg total lipid and 6.15+/-1.14 mg/dl, respectively) (P<0.05). Although plasma ascorbate and retinol levels were not significantly different between smokers and nonsmokers, smokers older than 45 years old had significantly lower plasma ascorbate levels (0.32+/-0.17 mg/dl) than age-matched nonsmokers (0. 53+/-0.14 mg/dl) (P=0.036). Higher level of plasma anti ox-LDL IgG was noted in the group of smokers compared with nonsmokers (515+/-409 mU/ml vs. 407+/-268 mU/ml, respectively) under the statistic method of Chi-Square test (P=0.049). A significant negative correlation was found between plasma anti ox-LDL IgG and alpha-tocopherol in the combined population as well as in the smoker group (r=-0.26, p=0.047; r=-0.48, p=0.006; respectively). However, there was no correlation between plasma anti ox-LDL IgG and the levels of other antioxidants. These results suggest that reduced concentrations of alpha-tocopherol are associated with cigarette smoking. The significantly negative correlation between plasma anti ox-LDL IgG and alpha-tocopherol in the entire study population as well as in the smoker group suggests that plasma alpha-tocopherol may be partially effective if not totally at protecting LDL from oxidative damage caused by cigarette smoking and dietary supplementation with alpha-tocopherol may provide a protective effect against LDL oxidation, especially in smokers.

Effects of veratrine and paeoniflorin on the isolated rat aorta.

The interactions and mechanisms between veratrine and paeoniflorin on the isolated rat aorta were studied. Veratrine (1x10(-6) to 1x10(-4) g/ml) could induce contraction on the isolated rat aorta in a concentration-related manner. Paeoniflorin had no effect on the isolated rat aorta. Pretreatment with prazosin (1x10(-6) M) and nifedipine (1x10(-6) M) but not yohimbine (1x10(-5) M) could decrease the tension of contraction induced by veratrine (1x10(-4) g/ml). Sodium nitroprusside (1x10(-4) M) could inhibit the contraction induced by veratrine (1x10(-4) g/ml) with or without endothelium, whereas methylene blue (5x10(-5) M) could increase the contraction induced by veratrine (1x10(-4) g/ml). Treatment with veratrine (1x10(-4) g/ml) could decrease the tension of contraction induced by norepinephrine (1x10(-6) M) or phenylephrine (1x10(-4) M). The inhibition of veratrine on norepinephrine-induced contraction was potentiated by L-arginine (1x10(-4) M) and reversed by L-NAME (1x10(-5) M). Paeoniflorin (1x10(-4) M) could decrease the tension of contraction induced by veratrine (1x10(-4) g/ml) and methylene blue (5x10(-5) M). The inhibition of paeoniflorin on veratrine was more potent on rat isolated aorta with endothelium than without endothelium. Ryanodine (1x10(-5) M) and Ca2+ -free medium could inhibit methylene blue-induced contraction. From the above results, the relaxation of veratrine on the norepinephrine-induced contraction might be related to the increase of NO and cGMP. The contraction of veratrine on the isolated rat aorta was via the increase of intracellular calcium which was inhibited by paeoniflorin.

Glucose and insulin infusion versus kayexalate for the early treatment of non-oliguric hyperkalemia in very-low-birth-weight infants.

Forty very low birth weight (VLBW) infants with non-oliguric hyperkalemia in the first few days after birth were enrolled in this study. They were randomly divided into 2 groups, regular insulin (RI) infusion group and kayexalate resin enema group. Therapy was administered when serum potassium level was greater than 6 mEq/L. None of these infants received blood transfusion during this study course. In RI group (n = 20), the ratio of infusion glucose to regular insulin was 10-15 gm glucose to 1 unit RI, and the glucose infusion rate was maintained at least 6 mg/Kg/min. In Kayexalate group (n = 20), the dose of Kayexalate was 1 gm/Kg body weight given rectally every four hours. All treatment discontinued after the serum potassium level returned to normal for 6 hours. The mean gestational ages were 27.4 +/- 1.8 weeks in RI group and 28.4 +/- 2.4 weeks in Kayexalate group, respectively. Mean birth weights were 935 +/- 259 gm (RI) and 1065 +/- 214 gm (Kayexalate). The ages at onset of hyperkalemia were 24.6 +/- 8.2 (RI) and 22.2 +/- 8.1 (Kayexalate) hours after birth. The mean urine outputs during the 8-hour interval prior to development of hyperkalemia were 5.4 +/- 1.3 (RI) and 5.5 +/- 0.9 (Kayexalate) ml/kg/min. The durations of hyperkalemia were 26.4 +/- 14.9 (RI) and 38.6 +/- 13.3 (Kayexalate) hours. The peak serum potassium levels during therapy were 7.3 +/- 0.9 and 7.4 +/- 0.6 mEq/L. The incidences of grade II and above intraventricular hemorrhage (IVH) were 15% (3/20) and 50% (10/20). The incidences of cardiac dysrhythmia were 5% (1/20) and 10% (2/20). Significantly shorter duration of non-oliguric hyperkalemia and lower incidence of IVH were noted in RI group, but there were no differences in the peak potassium level or the incidence of cardiac dysrhythmia between these two groups. We conclude that to use early continuous regular insulin infusion therapy for the treatment of non-oliguric hyperkalemia in VLBW infants is more effective than kayexalate in decreasing the duration of hyperkalemia and reducing the incidence of intraventricular hemorrhage.

Sister chromatid exchange in Chinese newborn infants treated with phototherapy for more than five days.

The frequency of sister chromatid exchange (SCE) was determined in newborn infants given phototherapy for more than five days, then determined again one year later. There were 8 healthy newborn infants and 15 icterus infants; 8 of these were treated with phototherapy for more than 5 days and the other 7 were not. In the follow-up study, 6 treated infants were evaluated. The results revealed that there was an increase in mean SCE frequency of peripheral lymphocytes after phototherapy, which reversed itself one year after treatment discontinuation. Prolonged continuous phototherapy may be responsible for the increase observed in SCEs in Chinese newborn.

Nonocclusive ischemic colitis following glycerin enema in a patient with coronary artery disease. A case report.

Acute colonic ischemia is the most common form of intestinal ischemia. Nonocclusive ischemic colitis contributes to some of these disorders. Heart disease, such as congestive heart failure, myocardial infarction, arrhythmias, aortic valve disease, and atherosclerotic cardiovascular disease, account for many of its risk factors. The majority of cases are associated with severe congestive heart failure with low cardiac output, or disease states resulting in dehydration, or the splanchnic vasoconstrictive effect of some medications. Reactive splanchnic vasoconstriction is responsible for nonocclusive ischemic colitis. Ischemic colitis induced by a cleansing enema has been reported once before. The authors present a case of coronary artery disease complicated by colonic ischemia following glycerin enema in preparation for coronary bypass surgery. Reactive inferior mesenteric artery spasm in response to the enema was noted in this case, rather than diffuse mesenteric artery spasm in response to low cardiac output state and vasoconstrictive drugs.

Clinical use of pentastarch in cardiac surgery without homologous blood transfusion.

In an attempt to avoid the use of homologous blood transfusion, we used pentastarch 6% or 10% in a consecutive series of open heart surgery. After induction of anesthesia, whole blood 500 cc was withdrawn from the patient via an artery line, and 6% or 10% pentastarch 500 cc was infused simultaneously via a central venous line. A further 500 cc pentastarch was placed in the heart-lung machine as a priming solution. After the operation the autologous blood was transfused. Pentastarch 500cc was also infused in the intensive care unit as a plasma expander. Significant improvements in cardiac output with decrease in hematocrit, plasma viscosity, systemic and pulmonary vascular resistance were noted after pentastarch infusion, due to its hemodiluting effects. Patients treated with pentastarch did not require transfusion of homologous blood, and they also displayed no abnormal coagulopathy, or increased amounts of postoperative bleeding during hospitalization. All patients were discharged without additional hospital stay. With the aid of pentastarch, acute normovolemic hemodilution can be performed safely in cardiac surgery with the advantages of saving stored blood, reducing the risks associated with homologous blood transfusion and profiting from hemodilution. It is therefore concluded that cardiac surgery can be performed safely with 6% or 10% pentastarch without any homologous blood transfusion.

Increased intracellular cyclic AMP levels suppress the mitogenic responses of human astrocytoma cells to growth factors.

It has been shown that the intracellular cAMP levels were decreased in human malignant astrocytomas. On the other hand, various growth factors and their receptors were found to be overexpressed in these tumors. It is therefore intriguing as to whether there is interplay between the two phenomena in the modulation of the astrocytoma cell growth. In a basal medium consisting of 75% DMEM, 25% Ham's F-12 supplemented with 2% FBS, we show that the mitogenic effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on human astrocytoma cells were suppressed by dibutyryl-cAMP. Dibutyryl-cAMP alone neither potentiated nor inhibited the tumor cell growth. Further studies show that PDGF-induced receptor autophosphorylation in human astrocytoma cells is suppressed by increased intracellular cAMP levels as measured by immunoprecipitation with anti-PDGF receptor and antiphosphotyrosine antibodies. Our results indicate that there is antagonistic interplay between the receptor tyrosine kinase pathway and cAMP-dependent protein kinase pathway in the control of the malignantly transformed glial cells. A reduced cAMP level seen in many human astrocytoma cells may favor their response to growth factor mitogenesis.

Acupuncture protection against experimental hyperbilirubinemia and cholangitis in rats.

Effects of acupuncture on experimental hyperbilirubinemia and cholangitis were studied in male rats (n = 33). The experimental group were treated with acupuncture, 18, 12 and 6 hr prior to and 6, 12 and 18 hr after oral administration of alpha-napthylisothiocyanate (ANIT, 100 mg per Kg). Rats were sacrificed 48 hours after challenge. Serum and liver samples were taken for biochemical and histological analysis, respectively. Results of this study revealed that rats treated with ANIT exhibited elevations in bilirubin, SGOT and SGPT as well as cholangitis. In rats receiving acupuncture and ANIT, biochemical and morphological parameters of liver injury were significantly reduced. Acupuncture therapy may be able to prevent ANIT-induced hyperbilirubinemia and cholangitis.

Protection by moxibustion against experimental hyperbilirubinemia and cholangitis in rats.

The effects of moxibustion on experimental hyperbilirubinemia and cholangitis were studied in male rats (n = 33). The experimental group were treated with moxibustion, 18, 12 and 6 hours prior to and 6, 12 and 18 hours after challenge with oral alpha-naphthylisothiocyanate (ANIT, 100 mg per kg). Rats were sacrificed 48 hours after challenge. Serum and liver samples were taken for biochemical and histological analysis, respectively. The results revealed that rats treated with ANIT exhibited elevations in bilirubin, SGOT and SGPT as well as cholangitis. In rats receiving moxibustion and ANIT, biochemical and morphological parameters of liver injury were significantly reduced. Thus, this study shows that moxibustion therapy may be able to prevent ANIT-induced hyperbilirubinemia and cholangitis.