Resolution and Absolute Configuration Assignment of a Natural Racemic Chromane from Peperomia obtusifolia (Piperaceae)

The resolution of the natural racemic chromane 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3 ''-methyl-2 ''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2H-1-benzopyran-6-carboxylic acid (1) isolated from the leaves of Peperomia obtusifolia has been accomplished using stereoselective HPLC. The absolute coil figuration of the resolved enantiomers was determined by the analysis of optical rotations and CD spectra. The finding of a racemic mixture instead of an enantiomerically pure metabolite raises questions about the final steps in the biosynthesis of this class of natural products, suggesting that the intramolecular chromane ring formation step may not be enzymatically controlled at all in P. obtusifolia. Chirality 21:799-801, 2009. (C) 2008 Wiley-Liss, Inc.

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine.

Pre-emptive epidural ketamine or S(+)-ketamine in post-incisional pain in dogs: A comparative study

Objective-To compare the pre-emptive analgesic effects of epidural ketamine or S(+)-ketamine on post-incisional hyperalgesia.Study Design-Prospective randomized study.Animals-Twenty-four mongrel dogs (1-5 years, weighing 11.9 +/- 1.8 kg).Methods-Dogs were anesthetized with propofol (5 mg/kg intravenously) and a lumbosacral epidural catheter was placed. Dogs were randomly allocated to 3 groups, each with 8 dogs. The control group (CG) was administered saline solution (0.3 mL/kg); the ketamine group (KG) ketamine (0.6 mg/kg); and the S(+)-ketamine group (SG) S(+)-ketamine (0.6 mg/kg). The final volume was adjusted to 0.3 mL/kg in all groups. Five minutes after the epidural injection a surgical incision was made in the common pad of the right hind limb and was immediately closed with simple interrupted nylon suture. Respiratory (RR) and heart (HR) rates, rectal temperature (7, sedation (S), lameness score, and mechanical nociceptive threshold by von Frey filaments were evaluated before the propofol anesthesia and at 15, 30, 45, 60, 75, and 90 minutes and then at 2, 4, 6, 8, 12, and 24 hours after epidural injection.Results-There were no differences in RR, HR, T, or S between groups. Motor blockade of the hind limbs was observed during 20 +/- 3.6 minutes in KG and during 30.6 +/- 7.5 minutes in SG (mean SD). Mechanical force applied to obtain an aversive response was higher from 45 minutes to 12 hours in KG and from 60 to 90 minutes in SG, when compared with CG.Conclusions-Pre-emptive epidural ketamine induced no alterations in RR and FIR, and reduced post-incisional hyperalgesia for a longer time than did S(+) ketamine.Clinical Relevance-Although anesthetic and analgesic potency of S(+) ketamine is twice that of ketamine, the racemic form is seemingly better for post-incisional hyperalgesia. (C) Copyright 2004 by the American College of Veterinary Surgeons.

Avaliação hemodinâmica e metabólica da cetamina e cetamina S(+) após a reposição volêmica com hidroxietilamido 130/0,4 e solução salina hipertônica 7,5%

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Relative potency of ketamine and S(+)-ketamine in dogs

The aim of this study was to determine the relative potency of racemic ketamine and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)-ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter with S(+)-ketamine. It was concluded that the potency ratio between ketamine and S(+)-ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.

Simultaneous analysis of the enantiomers of verapamil and norverapamil in rat plasma by liquid chromatography tandem mass spectrometry

An enantioselective micromethod for the simultaneous analysis of verapamil (VER) and norverapamil (NOR) in plasma was developed, validated and applied to the study of the kinetic disposition of VER and NOR after the administration of a single oral dose of racemic-VER to rats. VER, NOR and the internal standard (paroxetine) were extracted from only 100-mu L plasma samples using n-hexane and the enantiomers were resolved on a Chiralpak AD column using n-hexane:isopropanol: ethanol: diethyl ami ne (88:6:6:0.1) as the mobile phase. The analyses were performed in the selected reaction monitoring mode. Transitions 456 > 166 for VER enantiomers, 441 > 166 for NOR enantiomers and 330 > 193 for the internal standard were monitored and the method had a total chromatographic run time of 12 min. The method allows the determination of VER and NOR enantiomers at plasma levels as low as 1.0 ng/mL. Racemic VER hydrochloride (10 mg/kg) was given to male Wistar rats by gavage and blood samples were collected from 0 to 6.0 h(n = 6 at each time point). The concentration of (-)-(S)-VER was three folds higher than (+)-(R)-VER, with an AUC ratio (-)/(+) of 2.66. Oral clearance values were 12.17 and 28.77 L/h/kg for (-)-(S)-VER and (+)-(R)-VER, respectively. The pharmacokinetic parameters of NOR were not shown to be enantioselective. (c) 2007 Elsevier B.V. All rights reserved.

Semipreparative enantioseparation of methamidophos by HPLC-UV and preliminary in vitro study of butyrylcholinesterase inhibition

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Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Influence of N-Hexane Inhalation on the Enantioselective Pharmacokinetics and Metabolism of Verapamil in Rats

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Managing the dominant follicle in lactating dairy cows

Reproductive efficiency is not optimal in high-producing dairy cows. Although many aspects of ovarian follicular growth in cows are similar to those observed in heifers, there are numerous specific differences in follicular development that may be linked with changes in reproductive physiology in high-producing lactating dairy cows. These include: I) reduced circulating estradiol (E2) concentrations near estrus, 2) ovulation of follicles that are larger than the optimal size, 3) increased double ovulation and twinning, and 4) increased incidence of anovulation with a distinctive pattern of follicle growth in anovular dairy cows. The first three changes become more dramatic as milk production increases, although anovulation has not generally been associated with level of milk production. To overcome reproductive inefficiencies in dairy cows, reproductive management programs have been developed to synchronize ovulation and enable the use of timed AI in lactating dairy cows. Effective regulation of the CL, follicles, and hormonal environment during each part of the protocol is critical for optimizing these programs. This review discusses the distinct aspects of follicular development in lactating dairy cows and the methodologies that have been utilized in the past two decades in order to manage the dominant follicle during synchronization of ovulation and timed AI programs. (C) 2011 Published by Elsevier B.V.

Rapid configuration analysis of the solenopsins

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Double teeth in primary dentition: Report of two clinical cases

Odontogenic anomalies can occur as a result of conjoining or twinning defects. These include fusion, gemination and concrescence. This article presents two case reports of double teeth. In the first case reported, a 4-year-old white boy presented primary double teeth associated to the absence of the right permanent mandibular lateral incisor. In the second case, a 5-year-old white girl had a family history of anomaly in primary dentition. The girl and her mother presented double teeth in the primary dentition. Her mother showed hypodontia in the permanent dentition. Extra and intra oral clinical examination was made in both cases. Radiographic analyses showed the involvement of the permanent tooth. Authors conclude that double teeth in primary dentition have to be carefully analysed as they may be associated with anomalies in the permanent dentition. Correct diagnosis of the condition implicates in a better prognosis for the patient.

Further monoterpene chromane esters from Peperomia obtusifolia: VCD determination of the absolute configuration of a new diastereomeric mixture

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Absolute Configuration and Selective Trypanocidal Activity of Gaudichaudianic Acid Enantiomers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos cardiovasculares da anestesia dissociativa na reposição volêmica com colóide e solução hipertônica em cães: avaliação biotelemétrica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)