Preparation of alpha,beta-Unsaturated Diazoketones Employing a Horner-Wadsworth-Emmons Reagent

A new method for the preparation of alpha,beta-unsaturated diazoketones from aldehydes and a Horner-Wadsworth- Emmons reagent is reported. The method was applied to the short synthesis of two substituted pyrrolidines.

Bioreduction of alpha-chloroacetophenone by whole cells of marine fungi

The asymmetric reduction of 2-chloro-1-phenylethanone (1) by seven strains of marine fungi was evaluated and afforded (S)-(-)-2-chloro-1-phenylethanol with, in the best case, an enantiomeric excess of 50% and an isolated yield of 60%. The ability of marine fungi to catalyse the reduction was directly dependent on growth in artificial sea water-based medium containing a high concentration of Cl(-) (1.2 M). When fungi were grown in the absence of artificial sea water, no reduction of 1 by whole cells was observed. The biocatalytic reduction of 1 was more efficient at neutral rather than acidic pH values and in the absence of glucose as co-substrate.

Análise descritiva dos sistemas convectivos de escala meso-(alpha) através das imagens de satélite GOES-8

Na América do Sul há uma forte incidência de Sistemas Convectivos de Mesoescala (SCM), que na maioria das vezes, estão associados a desastres naturais. Estes causam impactos não só do ponto de vista meteorológico, mas também social e econômico. Neste trabalho analisa-se 49 Sistemas Convectivos de Meso-α, que atuam na América do Sul, durante os anos de 1999, 2000 e 2001. Com o auxílio de imagens do satélite GOES-8(canal IR, 10,4μm), identifica-se padrões comportamentais ao longo da vida dos SCM. Para a caracterização da evolução temporal e espacial, faz-se uma divisão da análise em duas partes: temporal e espacial. Na análise temporal, observam-se as variações rítmicas na intensificação da atividade convectiva. Na análise espacial, são observadas características como: tamanho e tempo de vida dos SCM e de seus respectivos núcleos distâncias entre os núcleos, trajetórias dos SCM entre outras características comportamentais dos núcleos convectivos que constituem o sistema. A análise dos dados mostra que mais da metade dos casos analisados sofrem dois tipos de variações na atividade convectiva, uma com período de 12 horas, e outra com menor periodicidade, 5,1 horas. Mostra-se que a evolução espacial dos SCM dá-se em média na direção das latitudes mais baixas, de forma discreta com o aparecimento de novos núcleos, na direção noroeste em relação ao núcleo antigo.

Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

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

TNF-alpha, H2O2 and NO response of peritoneal macrophages to Yersinia enterocolitica O : 3 derivatives

In this study, the effect of Yersinia derivatives on nitric oxide (NO), hydrogen peroxide (H2O2) and tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages was investigated. Addition of lipopolysaccharide (LPS) to the macrophage culture resulted in NO production that was dose dependent. on the other hand, bacterial cellular extract (CE) and Yersinia outer proteins (Yops) had no effect on NO production. The possible inhibitory effect of Yops on macrophage cultures stimulated with LPS was investigated. Yops partially inhibited NO production (67.4%) when compared with aminoguanidine. The effects of Yersinia derivatives on H2O2 production by macrophages were similar to those on NO production. LPS was the only derivative that stimulated H2O2 release in a dose-dependent manner. All Yersinia derivatives provoked the production of TNF-alpha, but LPS had the strongest effect, as observed for NO production. CE and Yops stimulated TNF-alpha production to a lesser extent than LPS. The results indicate the possibility that in vivo Yops may aid the evasion of the bacteria from the host defense mechanism by impairing the secretion of NO by macrophages. (C) 2003 Elsevier SAS. All rights reserved.

Synthesis, X-ray structure and antimycobacterial activity of silver complexes with alpha-hydroxycarboxylic acids

In this paper, synthesis, characterization and antimycobacterial properties of a new water-soluble complex identified as silver-mandelate are described. Elemental and thermal analyses are consistent with the formula [Ag(C6H5C(OH)COO)](n). The polymeric structure was determined by single X-ray diffraction and the two-dimensional structure is based on the bis(carboxylate-O,O') dimer [Ag-O, 2.237(3), 2.222(3) angstrom]. The structure is extended along both the b and c axes through two oxygen atoms of a bidentate alpha-hydroxyl-carboxylate residue [Ag-OH(hydroxyl), 2.477(3) angstrom; Ag-O(carboxylate), 2.502(3) angstrom; O-Ag-O, 63.94(9)degrees]. A strong d(10)-d(10) interaction was observed between two silver atoms. The Ag...Ag distance is 2.8307(15) angstrom. The NMR C-13 spectrum in D2O shows that coordination of the ligand to Ag(l) occurs through the carboxylate group in solution. Potentiometric titration shows that only species with a molar metaHigand ratio of 2:2 are formed in aqueous solution. The mandelate complex and the silver-glycolate, silver-malate and silver-hydrogen-tartarate complexes were tested against three types of mycobacteria, Mycobacterium avium, Mycobacterium tuberculosis and Mycobacterium kansasii, and their minimal inhibitory concentration (MIC) values were determined. The results show that the four complexes are potential candidates for antiseptic or disinfectant drugs for discharged secretions of patients affected with tuberculosis. (c) 2006 Published by Elsevier B.V.

Paracoccidioides brasifiensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P brasiliensis killing by human PMNs, and that H2O2 and Superoxide anion participate as effectors molecules in this process.

Progesterone concentrations, exogenous equine chorionic gonadotropin, and timing of prostaglandin F-2 alpha treatment affect fertility in postpuberal Nelore heifers

Two experiments were performed to test the hypothesis that elevated progesterone concentrations impair pregnancy rate to timed artificial insemination (TAI) in postpuberal Nelore heifers. In Experiment 1, postpuberal Nelore heifers (n = 398) received 2 mg estradiol benzoate (EB) and either a new progesterone-releasing intravaginal device containing 1.9 g of progesterone (CIDR) (first use) or a CIDR previously used for 9 d (second use) or for 18 d (third use) on Day 0, 12.5 mg prostaglandin F-2 alpha (PGF(2 alpha)) on Day 7, 0.5 mg estradiol cypionate (ECP) and CIDR withdrawal on Day 9, and TAI on Day 11. Largest ovarian follicle diameter was determined on Day 11. The third-use CIDR treatment increased largest ovarian follicle diameter and pregnancy rate. Conception to TAI was reduced in heifers with smaller follicles in the first- and second-use CIDR treatments, but not in the third-use CID treatment. In Experiment 2, postpuberal Nelore heifers received the synchronization treatment described in Experiment 1 or received 12.5 mg PGF2. on Day 9 rather than Day 7. In addition, 50% of heifers received 300 IU equine chorionic gonadotropin (eCG) on Day 9. Heifers were either TAI (Experiment 2a; n = 199) or Al after detection of estrus (Experiment 2b; n = 125 of 202). In Experiment 2a, treatment with cCG increased pregnancy rate to TAI in heifers that received PGF2. on Day 9 but not on Day 7 and in heifers that received a first-use CIDR but not in heifers that received a third-use CIDR. Treatments did not influence reproductive performance in Experiment 2b. In summary, pregnancy rate to TAI in postpuberal Nelore heifers was optimized when lower concentrations of cxogcnous progesterone were administered, and eCG treatment was beneficial in heifers expected to have greater progesterone concentrations. (C) 2009 Elsevier B.V. All rights reserved.

Elevated progesterone concentrations enhance prostaglandin F-2 alpha synthesis in dairy cows

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

Strategies to improve fertility in postpartum multiparous Bos indicus cows submitted to a fixed-time insemination protocol with gonadotropin-releasing hormone and prostaglandin F-2 alpha

In Exp. 1, we evaluated the effects of 2 lengths of progesterone exposure [CIDR (controlled intravaginal drug release); 7 vs. 14 d] before a modified CO-Synch protocol [50.0-mu g injection of GnRH 6.5 d before a 25.0-mg injection of PGF(2 alpha) followed by another injection of GnRH and fixed-time AI (TAI) 2 d after PGF(2 alpha)], with or without temporary weaning (TW) before GnRH treatments, on fertility of suckled multiparous Bos indicus cows (n = 283) and on calf performance. Timed AI pregnancy rates for cows receiving 7 d CIDR + TW, 7 d CIDR, 14 d CIDR + TW, and 14 d CIDR were 53, 47, 46, and 41%, respectively (P > 0.10). Calves submitted to two 48-h TW 6 d apart had decreased mean BW at 240 d (187.9 +/- 2.7 vs. 195.5 +/- 2.7 kg; P < 0.05), but BW at 420 d was not affected by TW (240.1 +/- 5.1 kg). In Exp. 2, we evaluated the effect of no treatment and treatment with or without a CIDR insert between GnRH and PGF(2 alpha) treatments of a modified CO-Synch protocol on pregnancy rate to TAI, and throughout a 90-d breeding season in suckled multiparous Bos indicus cows (n = 453). The inclusion of a CIDR between first GnRH and PGF(2 alpha) treatments of a modified CO-Synch protocol did not improve pregnancy rate (29 and 33% for cows receiving CO-Synch + CIDR and CO-Synch protocol, respectively), and cycling cows had poorer TAI pregnancy rates than anestrous cows treated with either synchronization protocol (21.7 vs. 40.7%; P < 0.05). However, regardless of treatment with CIDR, cows submitted to TAI protocol had greater (P < 0.05) pregnancy rates at 30 (54.8 vs. 11.2%), 60 (72.1 vs. 38.8%), and 90 d (82.0 vs. 57.9%) of breeding season than untreated cows.

Intermittent Therapy with 1,25 Vitamin D and Calcitonin Prevents Cyclosporin-Induced Alveolar Bone Loss in Rats

Bone loss associated with cyclosporin A (CsA) therapy can result in serious morbidity to patients. Intermittent administration of 1,25 Vitamin D and calcitonin reduces osteopenia in a murine model of postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of this therapeutic approach on CsA-induced alveolar bone loss in rats. Forty male Wistar rats were allocated to four experimental groups according to the treatment received during 8 weeks: (1) CsA (10 mg/kg/day, s.c.); (2) 1,25 Vitamin D (2 mu g/kg, p.o.; in weeks 1, 3, 5, and 7) plus calcitonin (2 mu g/kg, i.p.; in weeks 2, 4, 6, and 8); (3) CsA concurrently with intermittent 1,25 Vitamin D and calcitonin administration; and (4) the control treatment group (vehicle). At the end of the 8-week treatment period, serum concentrations of bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase (TRAP-5b), osteocalcin, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured and an analysis of bone volume, bone surface, number of osteoblasts, and osteoclasts was performed. CsA administration resulted in significant alveolar bone resorption, as assessed by a lower bone volume and an increased number of osteoclasts, and increased serum bone-specific alkaline phosphatase, TRAP-5b, IL-1 beta, IL-6, and TNF-alpha concentrations. The intermittent administration of calcitriol and calcitonin prevented the CsA-induced osteopenic changes and the increased serum concentrations of TRAP-5b and inflammatory cytokines. Intermittent calcitriol/calcitonin therapy prevents CsA-induced alveolar bone loss in rats and normalizes the production of associated inflammatory mediators.

Tumor Necrosis Factor alpha and Interleukin-1 beta Modulate Calcium and Nitric Oxide Signaling in Mechanically Stimulated Osteocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats

Salivation induced by intraperitoneal (i.p.) injections of pilocarpine (cholinergic agonist) is reduced by intracerebroventricular (i.c.v.) injections of moxonidine (alpha(2) adrenergic and imidazoline receptor agonist). In the present study, we investigated the involvement of central alpha(2) adrenergic receptors in the inhibitory effect of i.c.v. moxonidine on i.p. pilocarpine-induced salivation. Male Holtzman rats with stainless steel cannula implanted into the lateral ventricle (LV) were used. Saliva was collected using pre-weighted small cotton balls inserted into the animal's mouth under ketamine (100 mg kg(-1)) anesthesia. Salivation was induced by i.p. injection of pilocarpine (4 mu mol kg(-1)). Pilocarpine-induced salivation was reduced by i.c.v. injection of moxonidine (10 nmol) and enhanced by i.c.v. injections of either RX 821002 (160 nmol) or yohimbine (320 nmol). The inhibitory effect of i.c.v. moxonidine on pilocarpine-induced salivation was abolished by prior i.c.v. injections of the alpha(2) adrenergic receptor antagonists, RX 821002 (160 nmol) or yohimbine (160 and 320 nmol). The alpha(1) adrenergic receptor antagonist prazosin (320 nmol) injected i.c.v. did not change the effect of moxonidine on pilocarpine-induced salivation. The results suggest that moxonidine acts on central alpha(2) adrenergic receptors to inhibit pilocarpine-induced salivation, and that this salivation is tonically inhibited by central alpha(2) adrenergic receptors. (C) 2002 Elsevier B.V. All rights reserved.

Participation of alpha-1 and alpha-2 adrenoceptors of the lateral hypothalamic area in water intake, and renal sodium, potassium and urinary Volume excretion induced by central administration of angiotensin II

The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH, the present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV), the water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-l-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water, (C) 2000 Elsevier B.V.

Effects of castration on alpha(1)-adrenoceptor subtypes in the rat aorta

The expression of alpha(1)-adrenoceptor subtypes in several tissues is regulated by gonadal hormones. In this study, we investigated whether castration regulates the alpha(1)-adrenoceptor subtypes mediating the contractions of the aorta from male rats to noradrenaline. Noradrenaline induced similar concentration-dependent contractions in the aorta from control and castrated rats. Treatment of the aorta from both control and castrated rats with the alpha(1B)/alpha(1D)-adrenoceptor alkylating agent chloroethylclonidine resulted in approximate to1600-fold rightward shift in the concentration-response curves to noradrenaline. The pA(2) values found for WB 4101, benoxathian (alpha(1A)-selective) and BMY 7378 (alpha(1D)-selective) indicate that alpha(1D)-adrenoceptors are involved in the contractions of the aorta from control and castrated rats to noradrenaline. However, there was a 15-fold difference between the pK(B) estimated through the lowest effective concentrations of the alpha(1A)-adrenoceptor selective antagonist 5-methyl-urapidil in the aorta from control and castrated rats. The pK(B) estimated in aorta from control rats is consistent with the interaction with alpha(1D)-adrenoceptors (7.58 +/- 0.06), while that calculated in organs from control rats is consistent with alpha(1A)-adrenoceptors (8.76 +/- 0.09). These results suggest that castration induces plasticity in the alpha(1)-adrenoceptor subtypes involved in the contractions of the aorta to noradrenaline. (C) 2003 Elsevier B.V. All rights reserved.