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51.
J. Mendelson Reese T. Jones Susette Welm Matthew Baggott Isabella Fernandez Ann K. Melby Rajneesh P. Nath 《Psychopharmacology》1999,141(1):37-46
Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for
parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The
effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms
were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly,
subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1,
and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal
and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and
a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and
4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also
decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The
dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating
opiate dependence.
Received: 9 February 1998/Final version: 8 May 1998 相似文献
52.
R P Nath R A Upton E T Everhart P Cheung P Shwonek R T Jones J E Mendelson 《Journal of clinical pharmacology》1999,39(6):619-623
Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM-III-R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration-time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution. 相似文献
53.
The role of central histaminergic system in foot shock induced aggression was studied in mice. Histamine administered by intracerebral (IC) injection (25–200 g) produced a significant increase in fighting episodes in a dose dependent manner. It was observed that mepyramine (H1 blocker) given intraperitoneally (IP) significantly increased and metiamide (H2 blocker) given IC decreased significantly the fighting response. To determine the nature of receptors involved in histamine induced facilitation of aggressive behaviour, histamine was administered IC in mice pretreated with mepyramine or metiamide. Mepyramine pretreatment further increased the facilitatory effect of histamine while metiamide blocked the enhancement of aggressiveness by histamine. Combined pretreatment with metiamide and mepyramine decreased significantly the fighting counts which remained unaffected after histamine. Haloperidol did not block the enhancement of aggression by histamine or mepyramine. However, atropine pretreatment partially inhibited the histamine induced increase in the fighting counts. Results of pretreatment with metiamide and atropine were similar to those obtained with pretreatment of metiamide and mepyramine. Metiamide alone or in combination with atropine failed to affect the facilitatory effect of amphetamine on the foot-shockaggression. It is concluded that central histamine H2 receptors have a facilitatory role and H1 receptors an inhibitory role on aggressive behaviour in mice induced by foot-shock. Since histamine per se had a facilitatory effect on foot-shock induced aggression, the central H2 receptors seem to dominate over the H1 receptors. 相似文献
54.
Microvascular decompression for trigeminal neuralgia: report of outcome in patients over 65 years of age 总被引:5,自引:0,他引:5
Microvascular decompression (MVD) is now recognized as an effective operation for the cure of trigeminal neuralgia (TN), and is far superior to the other surgical procedures utilized in the treatment of TN. TN is common in the elderly, but there is debate concerning MVD in 'elderly' patients. Some clinicians have a policy of not offering patients over a certain age the choice of MVD, yet the recurrence rate is inversely related to the age of the patient. Previous failed procedures and a long period of pain before MVD, also affect the outcome negatively. This study is a retrospective review of the outcome in elderly patients following MVD. Forty-two patients over the age of 65 years are reviewed after undergoing MVD for TN. The results indicate that there was no serious morbidity or mortality that could be ascribed to old age and the length of stay in the hospital was not influenced by the age of the patient. The results are compared with the outcome in a younger age group and the literature on MVD for TN reviewed. 相似文献
55.
Francesco D’Errico Ph.D. Ravinder Nath Ph.D. Giovanni Silvano M.D. Luigi Tana D.Sc. 《International journal of radiation oncology, biology, physics》1998,41(5):1453
Purpose: A new technique is presented for in vivo measurements of the dose equivalent from photoneutrons produced by high-energy radiotherapy accelerators.Methods and Materials: The dosimeters used for this purpose are vials of superheated halocarbon droplets suspended in a tissue-equivalent gel. Neutron interactions nucleate the formation of bubbles, which can be recorded through the volume of gel they displace from the detector vials into graduated pipettes. These detectors offer inherent photon discrimination, dose-equivalent response to neutrons, passive operation, and small sensitive size. An in vivo vaginal probe was fabricated containing one of these neutron detector vials and a photon-sensitive diode. Measurements were carried out in patients undergoing high-energy x-ray radiotherapy and were also repeated in-phantom, under similar irradiation geometries.Results and Conclusion: Neutron doses of 0.02 Sv were measured in correspondence to the cervix, 50 cm from the photon beam axis, following a complete treatment course of 46.5 Gy with an upper mantle field of 18-MV x-rays. This fraction of dose from neutrons is measured reliably within an intense photon background, making the technique a valid solution to challenging dosimetry problems such as the determination of fetal exposure in radiotherapy. These measurements can be easily carried out with tissue-equivalent phantoms, as our results indicate an excellent correlation between in vivo and in-phantom dosimetry. 相似文献
56.
57.
Malaya Gupta Upal Kanti Mazumder Ramanathan Sambath Kumar Thangavel Siva Kumar 《Acta pharmacologica Sinica》2004,25(8):1070-1076
AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice. 相似文献
58.
Sodium trimetaphosphate enhances the effect of 250 p.p.m. fluoride toothpaste against enamel demineralization in vitro
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Emilene M. C. Missel Robson F. Cunha Ana E. M. Vieira Nathália V. S. Cruz Flavia C. N. Castilho Alberto C. B. Delbem 《European journal of oral sciences》2016,124(4):343-348
This in vitro study investigated the effect of sodium trimetaphosphate (TMP), added to toothpaste containing 250 p.p.m. fluoride, on enamel demineralization. Bovine enamel blocks (n = 96) were subjected to five pH cycles over a 7‐d period and treatment with suspensions of toothpastes containing 0, 250, 500, and 1,100 p.p.m. fluoride (as sodium fluoride), as well as with 250 p.p.m. fluoride containing TMP at 0.25, 0.5, 1.0, and 3.0%. Treatment with toothpaste suspensions was performed under agitation twice a day, for 1 min. Surface and cross‐sectional hardness, and fluoride firmly bound to enamel, were quantified. Data were subjected to one‐way anova , followed by Tukey's test. Low‐fluoride toothpastes containing TMP at 0.25–1.0% resulted in enamel mineral loss similar to that seen for the toothpaste containing 1,100 p.p.m. fluoride. Also, the addition of TMP to the toothpaste containing 250 p.p.m. fluoride promoted enamel fluoride concentrations similar to those obtained for the 500 p.p.m. fluoride group. The toothpaste containing 250 p.p.m. fluoride and 0.25% TMP led to the lowest mineral loss among all groups. It was concluded that the addition of as little as 0.25% TMP to a toothpaste containing 250 p.p.m. fluoride can reduce enamel demineralization to levels similar to those seen for a conventional toothpaste containing 1,100 p.p.m. fluoride, in vitro. 相似文献
59.
Anand Kumar Singh Manindra Nath Tiwari Om Prakash Mahendra Pratap Singh 《Current Neuropharmacology》2012,10(1):64-71
Cypermethrin, a class II pyrethroid pesticide, is used to control insects in the household and agricultural fields. Despite beneficial roles, its uncontrolled and repetitive applications lead to unintended effects in non-target organisms. Cypermethrin crosses the blood-brain barrier and induces neurotoxicity and motor deficits. Cypermethrin prolongs the opening of sodium channel, a major site of its action, leading to hyper-excitation of the central nervous system. In addition to sodium channel, cypermethrin modulates chloride, voltage-gated calcium and potassium channels, alters the activity of glutamate and acetylcholine receptors and adenosine triphosphatases and induces DNA damage and oxidative stress in the neuronal cells. Cypermethrin also modulates the level of neurotransmitters, including gamma-aminobutyric acid and dopamine. It is one of the most commonly used pesticides in neurotoxicology research not only because of its variable responses depending upon the doses, time and routes of exposure and strain, age, gender and species of animals used across multiple studies but also owing to its ability to induce the nigrostriatal dopaminergic neurodegeneration. This article describes the effect of acute, chronic, developmental and adulthood exposures to cypermethrin in experimental animals. The article sheds light on cypermethrin-induced changes in the central nervous system, including its contribution in the onset of specific features, which are associated with the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease models along with its advantages and pitfalls are also discussed. 相似文献
60.
Kavindra Nath David S. Nelson Andrew M. Ho Seung‐Cheol Lee Moses M. Darpolor Stephen Pickup Rong Zhou Daniel F. Heitjan Dennis B. Leeper Jerry D. Glickson 《NMR in biomedicine》2013,26(1):98-105
In vivo 31P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pHi) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pHe) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pHi decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post‐LND, with no significant change in pHe and a small transient decrease in bioenergetics (32.9 ± 10.6%, p > 0.05) at 40 min post‐LND. No changes in pHi or adenosine triphosphate/inorganic phosphate were detected in the brain (pHi, bioenergetics; p > 0.1) or skeletal muscle (pHi, pHe, bioenergetics; p > 0.1) for at least 120 min post‐LND. Steady‐state tumor lactate monitored by 1H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three‐fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log10 cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pHi and bioenergetics may sensitize melanoma to pH‐dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献