bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of growing rabbits fed concentrate and Stylosanthes (Verano) combinations under tropical conditions
Authors: IYEGHE‐ERAKPOTOBOR Grace Takpejewho
Published: January 2006

The performance of growing crossbred rabbits fed concentrate and Stylosanthes hamata (stylo) at different ratios was evaluated. The following ratios were used: 25:100, 50:75, 75:50, 100:25 and 125:10 (g : g; weight supplied per day). Total weight gain was lower and the feed : gain ratio (FGR) was higher with the 25:100 combination than with the other combinations. Daily feed intake significantly (P < 0.01) decreased, whereas feed cost and cost per kg intake increased as the concentrate level increased. Cost per kg gain increased with increases in concentrate levels up to 100 g before decreasing at 125 g. Weight gain, cost per kg intake and cost per kg gain had a quadratic relationship with concentrate level, whereas FGR and feed cost had a linear relationship. Time required to attain a market weight of 2.5 kg and total feed required to attain market weight decreased, whereas total cost of feeding increased with increases in concentrate level. Dry matter and ash digestibility were similar for all the treatments. Ether extract digestibility was lower for the 25:100 combination compared with the other treatments. Crude protein, nitrogen‐free extract digestibility and nitrogen retention were significantly lower for the 25:100 combination (0.74, 0.66 and 0.64) compared with the 100:25 combination (0.83, 0.75 and 0.79). The dressing percentage was similar for all treatments, whereas the proportion of live weight represented by the head increased with an increase in concentrate level. This study shows that rabbits are able to utilize leaf protein in stylo for growth even at the lowest level of concentrate.
Adrenocorticotropic hormone‐induced secretion of cortisol in goats is inhibited by androgen
Authors: MAEJIMA Yuko , AOYAMA Masato , KOBAYASHI Noriko , SUGITA Shoei
Published: January 2006

In a previous study, it was found that there are sex differences in goats with respect to the levels of cortisol secretion induced by transportation stress. We also found that treatment of castrated male goats with dihydrotestosterone (DHT) suppressed the increase in plasma cortisol concentration following transportation, but did not suppress the secretion of adrenocorticotropic hormone (ACTH). This suggests that androgen might block ACTH‐induced cortisol secretion. In order to examine this hypothesis, the effects of androgen on ACTH‐induced cortisol secretion in goats were investigated. First, castrated male goats were treated with testosterone (T), DHT or cholesterol (cho) for 21–25 days. Cho was used as a control for T and DHT treatment. Then, plasma cortisol concentrations were compared among the hormonal treatments after ACTH injection. Subsequently, the distribution of androgen receptors in the caprine adrenal gland was investigated. There were no differences in the basal cortisol concentrations among the hormonal treatments. However, plasma cortisol concentrations after ACTH injection were significantly lower in T‐ and DHT‐treated goats than in cho‐treated goats. Androgen receptors were present in 60% of the cells in the zonae fasciculata and reticularis of the adrenal cortex, the regions that secrete glucocorticoids. These results suggest that androgen may act directly on the adrenal cortex to suppress cortisol secretion induced by ACTH.
Effect of methionine hydroxy analog‐free acid on growth performance and chemical composition of liver of broiler chicks fed a corn–soybean based diet from 0 to 6 weeks of age
Authors: BUNCHASAK Chaiyapoom , KEAWARUN Natikan
Published: January 2006

The experiment was carried out to determine the effects of liquid DL‐methionine hydroxy analog‐free acid (LMA) and dry DL‐methionine (DLM) on growth performance, carcass quality and chemical composition of the livers of broiler chicks during 0–6 weeks of age. Four hundred and fifty male commercial broiler chicks (Ross strain) were used. The chicks were divided into three groups, and each group consisted of six replicates of 25 chicks each. The chicks were kept in floor pens, and water and feed were supplied ad libitum throughout the experiment. Three experimental diets were provided as follows: (i) corn–soybean‐based diet deficient in methionine; (ii) methionine‐deficient corn–soybean‐based diet supplemented with DLM to meet the methionine requirements of broiler chicks; and (iii) methionine‐deficient corn–soybean‐based diet supplemented with LMA (1.25‐fold (w/w) the amount of DLM supplied to the second group, given an assumption that 100 units of liquid LMA can be replaced by 80 units DLM to give similar performance results). During the starter period, the weight gains of chicks fed LMA or DLM were significantly greater than those in chicks receiving the methionine‐deficient diet (P < 0.05), and the addition of LMA significantly improved weight gain compared with the addition of DLM. Adding DLM or LMA significantly improved the feed conversion ratio (FCR) and percentage of uniformity (P < 0.05). No significant differences between the effects of DLM and LMA on these parameters were found. During the grower period (3–6 weeks of age), weight gain, FCR, uniformity and feed intake of chicks that received diet supplemented with DLM or LMA were superior to those of the methionine‐deficient group (P < 0.05). Chicks fed LMA had the same bodyweight gain and uniformity as those fed DLM. However, adding LMA resulted in a significant increase of FCR resulting from excess feed consumption. Outer breast meat yields were significantly improved and abdominal fat was significantly decreased when methionine sources were added (P < 0.05), and adding LMA tended to promote edible meat growth better than did adding DLM. Although no significant effects of methionine sources on the chemical composition of the liver were seen, adding methionine sources tended to increase liver fat content. In conclusion, it seems that the bioefficacy of LMA relative to DLM is not less than 80%. Therefore, chicks fed with diet supplemented with 1.25‐fold (w/w) as much LMA as DLM might exceed requirements for growth performance, while meeting requirements for meat production. Moreover, the relative bioefficacies of LMA and DLM between the starter and grower periods may perhaps be different.
Changes in walking parameters of milking cows after hoof trimming
Authors: AOKI Yasuhiro , KAMO Mikio , KAWAMOTO Hidenori , ZHANG Jianguo , YAMADA Akihisa
Published: January 2006

We examined the walking parameters of milking cows in relation to hoof trimming. The hooves of eight Holstein cows were trimmed. Two days before and after the hoof trimming, walking behavior, limb angles, back posture and vertical movement of the back while walking were measured. Walking rate (1.27 vs 0.87 m/s;P = 0.003), step length (1.46 vs 1.33 m;P = 0.009) and stepping rate (0.78 vs 0.65 steps/s;P = 0.046) were found to increase significantly after hoof trimming. Limb angles at the start and end of the support phase changed significantly after hoof trimming, thus indicating an improvement in the ‘on tiptoe’ appearance. The parameters relating to backline indicated that the marked arched shape of the back diminished after hoof trimming. Before hoof trimming, the positions of the withers varied widely and irregularly while walking; however, it changed after hoof trimming as the sinusoid curve and the range of vertical movement of withers decreased significantly. Overall, it has been quantitatively indicated that walking characteristics are improved after hoof trimming. The parameters used in the present study are expected to be useful for monitoring the walking characteristics of cows.
Polymerase chain reaction‐restriction fragment length polymorphism method for identifying carriers of hemophilia A in Japanese brown cattle
Authors: KHALAJ Maryam , ABBASI Abdol Rahim , TSUJI Takehito , MORITOMO Yasuo , SHIMOJO Kenichi , KUNIEDA Tetsuo
Published: January 2006

Hemophilia A is a severe congenital bleeding disorder characterized by subcutaneous hematoma and hemorrhage into muscles resulting from a deficiency of blood coagulation factor VIII. The authors have recently reported two cases of hemophilia A in Japanese Brown cattle and identified a nucleotide substitution in the factor VIII gene, resulting in an amino acid substitution of Leu to His, as a possible cause of the deficiency. In the present study, a simple and effective polymerase chain reaction (PCR)‐based diagnostic method was developed to identify carriers of this disorder, using a mismatch primer in combination with restriction enzyme digestion. The PCR reaction amplified a 118 bp fragment, which was not digested by the BspT104I restriction enzyme in affected animals but was digested into two fragments in normal animals. Both digested and undigested fragments were observed in carrier animals. This method was applied to identify the carriers of hemophilia A in a population of Japanese Brown cattle. By screening 155 DNA samples from Japanese Brown cattle, except for the dam of the two probands, no carriers were identified. It was therefore concluded that the probands represent isolated cases of hemophilia A, and that the frequency of the mutant allele in the Japanese Brown cattle population is very low.
Multi‐Modal and Tissue‐Differentiated Experimental Pain Assessment: Reproducibility of a New Concept for Assessment of Analgesics
Authors: Staahl Camilla , Reddy Hariprasad , Andersen Søren Due , Arendt‐Nielsen Lars , Drewes Asbjørn Mohr
Published: January 2006

Abstract: Experimental pain models for assessment of analgesic effect needs to be reproducible, valid and responding in a uniform way to changes in pain level. The pain system differs in various tissue types and analgesics may have different effects in different tissues. This study assessed the reproducibility of an experimental model using mechanical, thermal and electrical stimulations. Pain was evoked in three tissues: Skin, muscle and viscera. Pain was evoked and assessed in 24 healthy volunteers. The experiment was repeated three times with 30 min. intervals and twice with a weekly interval. Systematic bias, intra‐class correlation (ICC) and coefficient of variation (CV) and valid sample sizes for analgesic testing were assessed. The model proved to be feasible. Most tests were unbiased, showing stable means except for the mechanical and thermal stimulation in viscera, which showed decreasing pain thresholds when the tests were repeated with 30 min. intervals. Generally the pain tests showed relatively high CV (mean 71%, range 8–145%). The pain tests showed high ICC's (>0.80) when repeated on the same day. When the tests were repeated with an interval of one week, ICC was smaller (mean 0.79 range 0.49–0.96). This means that these tests are useful for analgesic testing recruiting useful sample sizes in a crossover (mean 31 range 2–84) and a parallel study (mean 59 range 3–164) design. Application of this experimental pain model in a cross‐over study design with appropriate base‐line recordings offers a unique opportunity of revealing analgesic effects on pain arising from different tissues.
Neurological Effects of White Spirit: Contribution of Animal Studies during a 30‐Year Period*
Authors: Nielsen Gunnar Damgård , Lund Søren Peter , Ladefoged Ole
Published: January 2006

Abstract: Numerous studies have suggested that long‐term occupational exposure to white spirit may cause chronic toxic encephalopathy (WHO 1996). This review summarizes the chronic nervous system effects of white spirit in animal studies during a 30‐year period. First, routine histopathology was consistently unable to reveal adverse peripheral or central nervous system effects after inhalation of white spirit. Second, neurobehavioural studies in animals showed no adverse effect after inhalation of white spirit with a high content of aromatics in contrast to what was found with products with a low content. Third, white spirit with a high content of aromatics induced adverse neurochemical changes at inhalation of 400 ppm and possibly already at 100 ppm. In the studied parameters, white spirit with a low content of aromatics showed no clear adverse neurochemical effects at inhalation of 400 ppm, but the neurophysiological tests showed adverse effects at this level. Fourth, neurophysiological methods may be more sensitive than histopathological, neurobehavioural and neurochemical methods. Overall, white spirit with a high and a low content of aromatics showed no overt difference in long‐term effects in animals, taking all studied end‐points into account. The differences in sensitivity of the test methods should be taken into consideration if new toxicological studies are conducted on this type of solvents.
Hepatoprotection of D‐Galactosamine‐Induced Toxicity in Mice by Purified Fractions from Garcinia kola Seeds
Authors: Adaramoye Oluwatosin A. , Adeyemi Edward O.
Published: January 2006

Abstract: The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D‐galactosamine (GalNH2). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin‐layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH2 (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH2‐only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH2‐induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal γ‐glutamyl transferase (γ‐GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH2‐intoxicated mice also restored glucose‐6‐phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH2‐intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione‐S‐transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH2‐induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH2‐induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.
Functional Characterization of Serotonin Receptor Subtypes in Human Duodenal Secretion
Authors: Engelmann Bodil Elisabeth , Bindslev Niels , Poulsen Steen Seier , Larsen Rune , Hansen Mark Berner
Published: January 2006

Abstract: Serotonin (5‐HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5‐HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5‐HT‐induced electrogenic ion transport in the duodenum of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5‐HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with airsuction for measurements of short‐circuit current by a previously validated technique. Short‐circuit current was measured before and after application of graded cumulative doses of 5‐HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5‐HT receptor antagonists: ketanserin, ondansetron, or SB‐204070 (1‐butyl‐4 piperidinmethyl‐8‐amino‐7‐chloro‐2,3‐dihydro‐1,4‐benzodioxin‐5‐carboxylate HCl). Histological examination was performed on duodenal biopsies. Helicobacter urease testing and histological examination determined Helicobacter pylori infection. 5‐HT induced a dose‐dependent and bumetanide‐sensitive short‐circuit current, which was independent of the presence of Helicobacter pylori infection. All the three 5‐HT receptor antagonists failed to significantly effect basal and 5‐HT‐induced short‐circuit current. Our results indicate that in human duodenum 1) 5‐HT is a potent stimulator of bumetanide‐sensitive secretion, 2) the serotonergic receptor subtype, which acts as the main mediator of 5‐HT‐induced secretion is different from the 5‐HT2, 5‐HT3, and the 5‐HT4 subtype and, 3) the sensitivity to 5‐HT is not altered by Helicobacter pylori infection.
Efficacy of Immediate and Subsequent Therapies against Soman‐Induced Seizures and Lethality in Rats
Authors: Myhrer Trond , Enger Siri , Aas Pål
Published: January 2006

Abstract: The purpose of the present study was to examine the efficacy of a triple combination of drugs with adequate anticonvulsant effects and a dual combination with inadequate anticonvulsant effects followed by adjunct therapy. The results showed that combined intramuscular injections of HI‐6 (42 mg/kg), atropine (14 mg/kg), and avizafone (3 mg/kg) administered 1, 16, and 31 min. after exposure to a soman dose of 4×LD50 completely terminated seizures with a moderate mortality rate (25%). When the soman dose was lowered to 3×LD50 the anticonvulsant effect was complete, and no rats died within 24 hr. Rats challenged with 5×LD50 of soman all died within 10 min. Without avizafone in the combination, seizures induced by 3 or 4×LD50 of soman could not be terminated unless an adjunct therapy consisting of procyclidine (6 mg/kg), diazepam (10 mg/kg), and pentobarbital (30 kg/kg) was given, and the mortality rate was comparatively high (78%). Administration of the adjunct therapy alone 6–16 min. after 4×LD50 of soman stopped the seizure activity, but all the rats died within 24 hr. Marked neuropathology was found in the piriform cortex and amygdala, whereas the hippocampal CA1 field was effectively protected when both the triple combination and the dual combination plus adjuncts had stopped seizures 35–55 min. after onset. It is concluded that termination of soman‐induced seizures at an early stage (<20 min.) is crucial to avoid neuronal pathology.
Protective Effect of Green Tea Extract and Tea Polyphenols against FK506‐Induced Cytotoxicity in Renal Cells
Authors: Hisamura Fumie , Kojima‐Yuasa Akiko , Kennedy David Opare , Matsui‐Yuasa Isao
Published: January 2006

Abstract:The nephrotoxicity induced by the immunosuppressive drug FK506 (tacrolimus or fujimycin), limits its usefulness in widespread application, and the underlying mechanism has not been completely understood. The primary targets of FK506 in the kidney are the proximal tubular epithelial cells. In this study, the protection of green tea extract against FK506‐induced cell death of LLC‐PK1 cells was investigated. FK506 caused a significant decrease in survival of the cells, but the addition of green tea extract reduced this effect in a dose‐dependent manner. Treatment of the cells with 50 μM (41.1 μg/ml) FK506 induced a significant increase in annexin V‐positive/propidium iodide‐negative cells from 2.68 to 14.5%, whereas the addition of 6.25, 12.5, and 25 μg/ml of green tea extract caused a significant protective effect in apoptotic cells from 14.5 to 6.51, 3.20 and 3.02%, respectively. The effect of five different constituent tea polyphenols was also examined. Epigallocatechin‐gallate and epigallocatechin significantly reduced FK506‐induced cytotoxicity but epicatechin and catechin had no effect on cell viability. Furthermore, changes in cytochrome c release and caspase activation, which characterize apoptosis, were studied. Epigallocatechin‐gallate and epigallocatechin suppressed a significant release of cytochrome c and activation of caspase‐3 in FK506‐treated LLC‐PK1 cells.
Effects of Methylated Derivatives of Luteolin Isolated from Cyperus alopecuroides in Rat H4IIE Hepatoma Cells*
Authors: Michels Gudrun , Mohamed Gamal A. , Weber Nadine , Chovolou Yvonni , Kampkötter Andreas , Wätjen Wim , Proksch Peter
Published: January 2006

Abstract: Polyphenols are ubiquitous substances in human diet. Their antioxidative, antiinflammatory and antiviral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. Luteolin is metabolized to glucuronides, but also to methylated derivatives. For example, O‐methylation of the catechol group mediated by the catechol‐O‐methyl transferase, is an important step in flavonoid metabolism. The aim of this project was to determine the effect of O‐methylation on antioxidative capacity and cytotoxicity of luteolin in H4IIE rat hepatoma cells. Therefore we analyzed the effects of luteolin 5,3′‐dimethylether, isolated from the flowers of foxtail flatsedge (Cyperus alopecuroides) and luteolin 5,7,3′,4′‐tetramethylether compared to the non‐methylated flavonoid luteolin. The antioxidative potential of luteolin was lowered by methylation, an effect that seems to be mediated by masking of the catechol moiety in the B ring. The cytotoxic potential of luteolin 5,3′‐dimethylether is comparable to luteolin, but the tetramethylether showed no cytotoxic effect. The cytotoxic effect of luteolin but not luteolin 5,3′‐dimethylether was mediated via apoptosis (caspase‐3 activation). We conclude that the O‐methylation of luteolin led to a decreased radical‐scavenging activity and to a reduction in the apoptotic potential of the flavonoid.
Inhibitory Effect of 5‐Fluorouracil on Cytochrome P450 2C9 Activity in Cancer Patients
Authors: Gunes Arzu , Coskun Ugur , Boruban Cem , Gunel Nazan , Babaoglu Melih O. , Sencan Orhan , Bozkurt Atila , Rane Anders , Hassan Moustapha , Zengil Hakan , Yasar Umit
Published: January 2006

Abstract:Drug interactions have been reported between 5‐fluorouracil and cytochrome P450 2C9 (CYP2C9) substrates, S‐warfarin and phenytoin. This study was performed to determine the influence of 5‐fluorouracil on cytochrome P450 2C9 (CYP2C9) activity in colorectal cancer patients (n=17) receiving 5‐fluorouracil. Losartan was used as a marker to assess CYP2C9 activity. Losartan and its CYP2C9 dependent metabolite, E‐3174, were determined in urine. The ratios of urinary losartan/E‐3174 before and after the 5‐fluorouracil treatment were compared for each patient. Genotyping was performed to detect theCYP2C9*2andCYP2C9*3.At the end of the first cycle of 5‐fluorouracil, losartan/E‐3174 ratio was increased by 28.0% compared to the pre‐treatment values (P=0.15). In five patients recruited for phenotyping after three 5‐fluorouracil cycles, the metabolic ratio was increased significantly by 5.3 times (P=0.03). The results suggest that in most patients 5‐fluorouracil inhibited CYP2C9 activity. This inhibition was more pronounced when the total administered dose increased. This finding may help explain the mechanism of interaction between 5‐fluorouracil and CYP2C9 substrates.
Accidental Ten Times Overdose Administration of Recombinant Human Erythropoietin (rh‐EPO) up to 318,000 Units a Day in Acute Myocardial Infarction: Report of Two Cases
Authors: Shin Dae‐Hee , Kwon Young‐Il , Choi Sung‐Il , Park Ui‐Soon , Lee Je , Shin Jin‐Ho , Lee Jae‐Ung , Kim Soon‐Gil , Kim Jeong‐Hyun , Lim Heon‐Kil , Lee Bang‐Hun , Kim Kyung‐Soo
Published: January 2006

Abstract: The cytokine erythropoietin protects the heart from ischaemic injury, in part by preventing apoptosis. But appropriate dose of erythropoietin for the protection of injured heart has not been studied. While we were researching the cardiac protective effects of erythropoietin in acute myocardial infarction, we experienced two cases of accidental nearly ten times overdose administration of erythropoietin up to 318,000 units instead of 33,000 units on the second day of three scheduled days of treatment. So a total of 384,000 units of erythropoietin were administered during three days. In case 1, the ALT level soared up to 386 U/l on the second day of administration and decreased slowly. It was back to normal state 3 months later. The AST level increased slowly up to 391 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.7 g/dl (14.7 g/dl at admission) and, 3 months later, normalized to 14.8 g/dl. In case 2, the ALT level was elevated up to 98 U/l on the second day of administration and decreased slowly. Three months later, the ALT level was normalized. The AST level also increased slowly up to 71 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.6 g/dl (13.8 g/dl at admission) and, 3 months later, normalized to 13.6 g/dl. In these two cases reported, these patients, even after massive overdose, tolerated it relatively well and the only side‐effects we found were elevated liver enzyme and haemoglobin levels.
Contrasting Changes in Phase I and Phase II Metabolism of Acetaminophen in Male Mice Pretreated with Carbon Tetrachloride
Authors: Yim Hye K. , Jung Young S. , Kim Sung Y. , Kim Young C.
Published: January 2006

Abstract: Effect of carbon tetrachloride (CCl4) pretreatment on the biotransformation and elimination of acetaminophen were examined in male mice. A 24 hr initial dose of CCl4 (0.05 ml/kg, intraperitioneally) reduced the induction of hepatotoxicity resulting from acetaminophen treatment (350 mg/kg, intraperitoneally) as determined by changes in serum alanine and aspartate aminotransferase, and sorbitol dehydrogenase activities. Acetaminophen and the major metabolites in plasma were monitored for 12 hr following acetaminophen treatment. CCl4 pretreatment decreased the plasma concentrations of acetaminophen‐cysteine and acetaminophen‐mercapturate, but acetaminophen‐glucuronide and acetaminophen‐sulfate were increased significantly. The elimination of the parent drug from plasma was not affected by CCl4. In urine collected for 24 hr, the concentrations of acetaminophen‐sulfate and acetaminophen‐glucuronide were increased by 84% and 33%, respectively, whilst acetaminophen‐cysteine and acetaminophen‐mercapturate were reduced to approximately one third of control. Expression of cytochrome P450 (CYP) isozymes was determined using antibodies of 2E1 and 1A2 as probes. CYP2E1 and 1A2 expressions were decreased significantly by CCl4. Likewise, CCl4 treatment reduced the microsomal p‐nitrophenol hydroxylase and p‐nitroanisole O‐demethylase activities to less than one third of control. The results indicate that, although CCl4 reduces the generation of thioether conjugates of acetaminophen by decreasing the CYP activities, inhibition of the oxidative metabolism of acetaminophen is counterbalanced by the enhancement of conjugate formation via the glucuronide and sulfate pathways, resulting in elimination of the drug at a rate equivalent to that in normal mice. It is suggested that liver injury in patients may not warrant a mandatory reduction of drug doses extensively inactivated via phase II reactions.
The Endocannabinoid System: Current Pharmacological Research and Therapeutic Possibilities
Authors: Jonsson Kent‐Olov , Holt Sandra , Fowler Christopher J.
Published: January 2006

Abstract: In the relatively short period of time since the discovery of cannabinoid receptors and their endogenous ligands, the endocannabinoids, an intensive research effort has resulted in the identification of agents that affect all aspects of the endocannabinoid system. The cannabinoid1 receptor antagonist rimonabant is in phase III clinical trials for the treatment of obesity and as an aid to smoking cessation, and cannabinoid2 receptor agonists are promising in animal models of inflammatory and neuropathic pain. In the present MiniReview, the endocannabinoid system is described from a pharmacological perspective. The main topics covered are: the mechanism of action of cannabinoid2 receptor agonists; identification of the endocannabinoid(s) involved in retrograde signalling; the elusive mechanism(s) of endocannabinoid uptake; therapeutic possibilities for fatty acid amide hydrolase inhibitors; and the cyclooxygenase‐2 and lipoxygenase‐derived biologically active metabolites of the endocannabinoids.
Molecular markers of phase transition in locusts
Authors: DE LOOF ARNOLD , CLAEYS ILSE , SIMONET GERT , VERLEYEN PETER , VANDERSMISSEN TIM , SAS FILIP , HUYBRECHTS JURGEN
Published: January 2006

Abstract
The changes accompanying the transition from the gregarious to the solitary phase state in locusts are so drastic that for a long time these phases were considered as distinct species. It was Boris Uvarov who introduced the concept of polyphenism. Decades of research revealed that phase transition implies changes in morphometry, the color of the cuticle, behavior and several aspects of physiology. In particular, in the recent decade, quite a number of molecular studies have been undertaken to uncover phase‐related differences. They resulted in novel insights into the role of corazonin, neuroparsins, some protease inhibitors, phenylacetonitrile and so on. The advent of EST‐databases of locusts (e.g. Kang et al., 2004) is a most encouraging novel development in physiological and behavioral locust research. Yet, the answer to the most intriguing question, namely whether or not there is a primordial molecular inducer of phase transition, is probably not within reach in the very near future.
Laboratory evaluation of the toxic properties of forest anchomanes, Anchomanes difformis against pulse beetle Callosobruchus maculatus (Coleoptera: Bruchidae)
Authors: AKINKUROLERE ROTIMI O. , ADEDIRE CHRIS O. , ODEYEMI OLUSOLA O.
Published: January 2006

Abstract
Laboratory experiments were carried out to investigate the efficacy of crude stem extracts of forest anchomanes, Anchomanes difformis (P. Beauv.) a plant occurring in West African forests, against the pulse beetle Callosobruchus maculatus (Fabricius). Crude stem extracts at 3% concentration showed high contact toxicity to adult beetles within 24 h after application, while it was moderately toxic to the beetles at the lowest (1%) concentration. At the highest application rate, the plant extract provided good protection to grains stored for 90 days. Grain viability and water absorption capacity were not affected by treatments with ethanol extracts of A. difformis. The significance of these findings is discussed in relation to biopesticide‐means of controlling cowpea bruchids.
Accumulation of cadmium and its effects on growth, development and hemolymph biochemical compositions in Boettcherisca peregrina larvae (Diptera: Sarcophagidae)
Authors: WU GUO‐XING , YE GONG‐YIN , HU CUI , CHENG JIA‐AN
Published: January 2006

Abstract
Newly emerged larvae of the fleshfly, Boettcherisca peregrina were exposed to two different CdCI2 concentrations of 100 μg/g and 400 mg/g diet fresh weight (DFW). They were administered in the diets until the end of larval stage. Cd‐exposed larvae accumulated significant amounts of Cd and this accumulation increased with the exposure dose and time. The body weights were lightened and lengths of larvae were shortened considerably after Cd exposure, especially at the higher Cd concentration. The total larval duration was also extremely affected due to Cd exposure. The average duration was prolonged significantly by 14 h at the lower Cd concentration, while it was increased by 33.7 h over controls at the higher Cd concentration. A significant decrease in contents of either soluble proteins, total lipids or caloric values in the hemolymph occurred due to Cd exposure throughout the entire tested period but after 120 h of Cd exposure. In contrast, when exposed to Cd with its higher concentration, total sugar contents in the hemolymph were increased strikingly over the whole tested time, except after 96 h of Cd exposure, while they were not apparently altered except after 24 h of Cd exposure at the lower concentration. Thus, it is suggested that Cd exposure shows significant adverse impact on the growth and development, as well as metabolism, in larvae of this fleshfly, depending on its exposure time and dose.
Toxicological and biochemical characterizations of malathion sensitivity in two field populations of Oxya chinensis (Orthoptera: Acridoidea)
Authors: YANG MEI‐LING , WU HAI‐HUA , GUO YA‐PING , MA EN‐BO
Published: January 2006

Abstract
We evaluate comparative toxicity of malathion in the two populations of the grasshopper Oxya chinensis, collected from Daixian and Fanshi of Shanxi province, China. General esterases and acetylcholinesterase (AChE) from the two populations were characterized and compared. LD50 of the Daixian population (7.58 μg/g body weight) was 2.02‐fold higher than that of the Fanshi population (3.75 μg/g body weight). General esterase‐specific activities in the Daixian population were 1.91, 1.10 and 1.85‐fold higher than those in the Fanshi population, when α‐NA, α‐NB and β‐NA were used as a substrate, respectively. Kinetic studies of general esterase showed that Vmax values of general esterases hydrolyzing α‐NA, α‐NB and β‐NA in the Daixian population were 2.15‐, 1.12‐, and 1.47‐fold, respectively, higher than those in the Fanshi population. The AChE activity of the Fanshi population was 1.54‐fold higher than that of the Daixian population. Kinetic analysis of AChE showed that significant differences were presented between the two populations in the Km values; and the Vmax value in the Fanshi population was higher than that in the Daixian population. Inhibition studies of AChE indicated that AChE from the Daixian population was 2.56‐, 2.80‐, and 2.29‐fold less sensitive to inhibition by paraoxon, chlorpyrifos‐oxon, and demeton‐S‐methyl, respectively, than that from the Fanshi population. These biochemical characterizations of general esterases and AChE were consistent with malathion bioassay in the two populations. It is inferred that the reduced sensitivity of altered AChE and increased general esterase activities play an important role in the differences of insusceptibility of Oxya chinensis to malathion between the two populations.
Resistance and susceptibility of alfalfa (Medicago sativa L.) cultivars to the aphid Therioaphis maculata (Homoptera: Aphididae): insect biology and cultivar evaluation
Authors: DE ALMEIDA E SILVA ALEXANDRE , VARANDA ELENICE MOURO , BAROSELA JOSÉ RICARDO
Published: January 2006

Abstract
Biology of the aphid Therioaphis maculata was studied on alfalfa (Medicago sativa L.), including four resistant (Mesa‐Sirsa, CUF101, Baker and Lahontan) and two susceptible (ARC and Caliverde) alfalfa cultivars, and one of the most cropped Brazilian cultivars, Crioula. Under controlled conditions, antibiosis (i.e., reduced longevity, fecundity and increased mortality of the aphid) was observed mainly on the resistant alfalfa cultivars, except on Lahontan. Crioula seemed to be tolerant to aphids. Present data support geographic limitation usage of cultivars, and we suggest Baker and Mesa‐Sirsa as sources of antibiosis, and provide biological information of a tropical T. maculata biotype on alfalfa.
Lack of repellency of three commercial ultrasonic devices to the German cockroach (Blattodea: Blattellidae)
Authors: HUANG FANGNENG , SUBRAMANYAM BHADRIRAJU
Published: January 2006

AbstractThree commercial ultrasonic devices (A, B, and C) were tested for their ability to repel the German cockroach,Blattella germanica(L.) (Blattodea: Blattellidae), in Plexiglas® enclosures. Device A generated peak frequencies at 26 kHz and 34 kHz, and produced a 95 ± 1 dB sound pressure level (SPL) at 50 cm distance (0 dB = 20 log10[20 μPa/ 20 μPa]). Device B generated peak frequencies at 27 kHz and 35 kHz, and produced a 92 ± 4 dB SPL. Device C generated a wide range of frequencies between 28–42 kHz and produced an 88 ± 2 dB SPL. Ultrasound from any of the three devices did not demonstrate sufficient repelling ability against the German cockroach in the tests. The result failed to provide evidence that ultrasonic technology could be used as an effective pest management tool to repel or eliminate the German cockroach.
Role of Perivascular Cells and Myocytes in Vascular Amyloidosis
Authors: WISNIEWSKI H. M. , WEGIEL J. , VORBRODT A. W. , MAZUR‐KOLECKA B. , FRACKOWIAK J.
Published: January 2006

Abstract: Amyloidogenic processing of amyloid‐β precursor protein (APP) by cells of the brain is the major pathologic component of Alzheimer's disease. Amyloid‐β (Aβ) is of heterogenous origin. Perivascular cells of monocyte‐macrophage‐microglial cell lineage produce fibrillar Aβ in the wall of capillaries, whereas parenchymal microglial cells produce fibrillar Aβ in the parenchyma of gray matter. Fibrillar Aβ deposition by perivascular cells leads to endothelial cell degeneration and death, obliteration of affected capillaries, and reduction of the length of the vascular network. These changes cause local ischemia with neuronal degeneration and death. Smooth muscle cells are the source of Aβ in the tunica media of parenchymal and leptomeningeal arteries and veins. Fibrillar Aβ in the tunica media of leptomeningeal and parenchymal vessels causes degeneration and necrosis of smooth muscle cells and leads to multiple cortical hemorrhages. Smooth muscle cells isolated from blood vessels with amyloid deposits secrete Aβ and accumulate nonfibrillar Aβ intracellularly. The amyloidogenic processing of APP can be enhanced by apolipoprotein E, reduced by transthyretin, and modulated by several cytokines.
Linguistic Ability in Early Life and the Neuropathology of Alzheimer's Disease and Cerebrovascular Disease: Findings from the Nun Study
Authors: SNOWDON D. A. , GREINER L. H. , MARKESBERY W. R.
Published: January 2006

Abstract: Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were −0.59 for the frontal lobe, −0.48 for the temporal lobe, and −0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.
Cerebrovasculature‐mediated Neuronal Cell Death
Authors: GRAMMAS PAULA , REIMANN‐PHILIPP ULRICH , WEIGEL PAUL H.
Published: January 2006

Abstract: The presence of significant vascular disease in patients with Alzheimer's disease (AD) and the recognition of the ApoE genotype as a risk factor for both coronary disease and AD support an association between AD and vascular disease. It is our hypothesis that brain microvessels contribute to the pathogenesis of AD by producing soluble factors that injure or kill neurons. In this study we report that AD microvessels produce factors that are noxious to neurons and that these vessels can evoke neuronal cell death in vitro. In these experiments, microvessels are isolated from the cerebral cortices of AD patients and nondemented elderly and young controls. Microvessels isolated from AD brains produce high levels of a known neurotoxin nitric oxide, compared to vessels from aged‐matched controls. In addition, we demonstrate a direct neurotoxic effect of AD microvessels when co‐cultured with primary rat cerebral cortical neurons. In contrast, vessels from elderly non‐demented donors are less lethal, and brain vessels from younger donors are not neurotoxic. Similarly, AD vessels exhibit a dose‐dependent toxicity in co‐culture with the human neurons. Finally, treatment of AD microvessels with the protein synthesis inhibitor cycloheximide reduces AD vessel neurotoxicity, suggesting that the neurotoxic factor is a protein. These findings suggest that the cerebral microvasculature is a source of factors that can injure neurons and implicate a novel mechanism of vascular‐mediated neuronal cell death in AD.
Cerebrovascular Smooth Muscle Cell Surface Fibrillar Aβ: Alteration of the Proteolytic Environment in the Cerebral Vessel Wall
Authors: VAN NOSTRAND WILLIAM E. , MELCHOR JERRY , WAGNER MATTHEW , DAVIS JUDIANNE
Published: January 2006

Abstract: Cerebrovascular deposition of the amyloid b‐protein (Aβ) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders including hereditary cerebral hemorrhage with amyloidosis Dutch‐type (HCHWA‐D). Aβ deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Aβ deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. Recent studies from our laboratory have shown that cell‐surface assembly of Aβ into fibrillar structures causes cellular degeneration via an apoptotic pathway and creates an altered proteolytic microenvironment on the cell surface of human cerebrovascular smooth muscle cells (HCSM cells). For example, HCSM cell‐surface Aβ fibrils serve as a site for tight binding of cell‐secreted amyloid β‐precursor protein (AβPP). Since AβPP is a potent inhibitor of key proteinases of coagulation cascade, its enhanced localization on the Aβ fibrils would provide an strong anticoagulant environment. In addition, HCSM cell‐surface Aβ fibrils are potent stimulators of tissue plasminogen activator (tPA) creating a profibrinolytic milieu. Our findings indicate that Aβ fibril assembly on the HCSM cell surface causes cellular degeneration and results in both a strong anticoagulant and fibrinolytic environment. Together, these altered proteolytic events could create a setting that is conducive to loss of vessel wall integrity and hemorrhagic stroke.
Aβ Vasoactivity: An Inflammatory Reaction
Authors: PARIS DANIEL , TOWN TERRENCE , PARKER TIMOTHY , HUMPHREY JAMES , MULLAN MICHAEL
Published: January 2006

Abstract: Mounting evidence from in vitro and in vivo studies in transgenic mice overproducing β‐amyloid peptides (Aβ) suggests that Aβ can induce vasoconstriction and decrease cerebral blood flow. In this report, we describe the vasoactive properties of Aβ, in particular the enhancement of endothelin‐1‐induced vasoconstriction and Aβ's induction of a long‐lasting vasoconstrictive event. Furthermore, we show that low doses (as low as 50 nM) of freshly solubilized Aβ similar to those observed in the plasma of patients suffering from Alzheimer's disease are vasoactive. By using various inhibitors and activators of the phospholipase A2 (PLA2)/arachidonic acid (AA) cascade, we demonstrate that Aβ vasoactivity is dependent on activation of this intracellular signaling pathway, resulting in stimulation of downstream cyclooxygenase‐2 and 5‐lipoxygenase, which mediate production of proinflammatory eicosanoids. Taken together, our data show that Aβ directly activates an intracellular proinflammatory pathway, which is responsible for its vasoactive properties.
Cerebral Amyloid Angiopathy: Accumulation of Aβ in Interstitial Fluid Drainage Pathways in Alzheimer's Disease
Authors: WELLER ROY O. , MASSEY ADRIAN , KUO YU‐MIN , ROHER ALEX E.
Published: January 2006

Abstract: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β‐amyloid (Aβ) peptides in the walls of arteries both in the cortex and meninges. Here, we test the hypothesis that CAA results from the progressive accumulation of Aβ in the perivascular interstitial fluid drainage pathways of the brain. Experimental studies have shown that interstitial fluid (ISF) from the rat brain flows along periarterial spaces to join the cerebrospinal fluid (CSF) to drain to cervical lymph nodes. Such lymphatic drainage plays a key role in B‐cell and T‐cell mediated immunity of the brain. Anatomical studies have defined periarterial ISF drainage pathways in the human brain that are homologous with the lymphatic pathways in the rat brain but are largely separate from the CSF. Periarterial channels in the brain in man are in continuity with those of leptomeningeal arteries and can be traced from the brain to the extracranial portions of the internal carotid arteries related to deep cervical lymph nodes. The pattern of deposition of Aβ in senile plaques and in CAA suggests that Aβ accumulates in pericapillary and periarterial ISF drainage pathways. Aβ could accumulate in CAA due to either (i) increased production of Aβ, (ii) reduced solubility of Aβ peptides, or (iii) impedance of drainage of Aβ along periarterial ISF drainage pathways within the brain and leptomeninges due to aging factors in cerebral arteries. Elucidation of factors that reduce elimination of Aβ via perivascular drainage pathways may lead to their rectification and to new strategies for treatment of Alzheimer's disease.
Prospects for Noninvasive Imaging of Brain Amyloid β in Alzheimer's Disease
Authors: FRIEDLAND R. P. , SHI J. , LAMANNA J. C. , SMITH M. A. , PERRY G.
Published: January 2006

Abstract:The brain in patients with Alzheimer's disease (AD) contains large amounts of fibrillary amyloid β protein. Studies attempting to use levels of amyloid β protein in plasma, cerebrospinal fluid or skin as diagnostic tests for the disease have not been fruitful. A method for the noninvasive detection of cerebral amyloid β would be valuable for dementia differential diagnosis, pathophysiology and monitoring of anti‐amyloid therapies. Anti‐amyloid monoclonal antibody 10H3 has been evaluated as an amyloid‐imaging ligand, without success. Important considerations in the development of amyloid‐imaging ligands include choice of radiolabel and physical and biological half‐lives, route of administration, protein binding, use of control molecules, and imaging techniques. It is important that imaging studies be designed to reflect the slow nature of the process of amyloid deposition. We used a transgenic mouse model overexpressing β protein precursor (βPP) to assess the binding of basic fibroblast growth factor (bFGF) and serum amyloid P compo nent (SAP) to amyloid β (Aβ) plaques in mouse brain. Although the binding of these ligands is similar to AD, neither is found endogenously associated with Aβ deposits. Because SAP is a component of mouse serum, these findings suggest the blood‐brain barrier in transgenic mice is not affected as it is in AD. These findings suggest that the transgenic mouse may be used as a model for evaluation of Aβ imaging methods.