Sodium Butyrate Downregulates Implant-Induced Inflammation in Mice.

Sodium butyrate (NaBu), a histone deacetylase inhibitor, has shown to exert beneficial actions attenuating inflammation in a number of intestinal and extra-intestinal diseases. However, the effects of NaBu on persistent inflammatory processes as in a response to implantation of foreign material have not been investigated. Synthetic matrix of polyether-polyurethane sponge was implanted in mice's subcutaneous layer of the dorsal region, and the animals were treated daily with oral administration of NaBu (100 mg/kg). After 7 days, the implants were removed and processed for assessment of inflammatory markers. Butyrate treatment caused a significant attenuation of neutrophil and macrophage infiltration in implants, which was reflected by the reduction of myeloperoxidase and N-acetyl-ß-D-glucosaminidase activities, respectively. Similar reduction was observed in intra-implants nitrite levels of NaBu-treated mice. NaBu treatment was also able to decrease mast cell recruitment/activation and the levels of CXCL1, CCL2, IL-6, TNF-ɑ, and TGF-ß1 in the implants but did not alter the levels of IL-10. In addition, NaBu administration decreased the concentration of proteins p65 and p50 in the nucleus as compared with the cytoplasm by western blot analysis. This result suggests that treatment with NaBu inhibited the NF-κB pathway. The circulating levels of TNF-ɑ and TGF-ß1 were also attenuated by NaBu. Persistent inflammation at sites of implanted devices very often impairs their functionality; therefore, our findings suggest that NaBu holds potential therapeutic value to control this adverse response to biomedical implants.

Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat

Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The pressent study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 µg/kg) or electrical stimulation at increasing frequencies (0.1 - 3 Hz) were evaluated before and during continous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1 - 10 µg/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure but not those in heart rate - produced by stimulation of the appropriate spinal segments. Theses effects of 5-HT were more prononced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents

Inhalational anesthetics: desflurane and sevoflurane.

This article reviews the physico-chemical properties and performance characteristics of the two new potent inhaled anesthetics, desflurane and sevoflurane. Both drugs provide a greater degree of control of anesthetic depth and a more rapid immediate recovery from anesthesia than is currently available with other inhaled agents because of their decreased solubility. Desflurane is currently in widespread clinical use in the United States and parts of Europe. Compared with sevoflurane, it has the additional advantage of being extremely resistant to degradation and biotransformation. However, its pungent odor and tendency to irritate the respiratory tract make it unsuitable for inhalational inductions, and it has been linked to CO production in CO2 absorbents. The sympathetic nervous system activation that occurs with desflurane limits its use in patients with cardiac disease. Otherwise, its hemodynamic and physiologic effects are similar to those seen with isoflurane. Studies of the economics of using desflurane are mixed, although it may offer the advantage of shorter postoperative recovery time. Sevoflurane is currently in widespread clinical use in Japan and parts of South America. The FDA Advisory Panel has recently recommended approval of sevoflurane in the United States, and we can expect the drug to be clinically available in the United States in the second quarter of 1995. Compared with desflurane, sevoflurane has the additional advantage of being nonirritating to the airway; inhalational induction of anesthesia with sevoflurane is achieved rapidly and easily. The instability of sevoflurane with CO2 absorbents and its in vivo biotransformation produce potentially toxic byproducts. These byproducts, including Compound A and fluoride, have been extensively studied, and although the possibility for iatrogenic sequelae from sevoflurane exists, the likelihood of long-term toxicity appears quite low. Phase IV studies are indicated to determine the safety of administering sevoflurane (1) to renally impaired patients and (2) to any patient with fresh gas flows less than 2 L/min. Sevoflurane is otherwise very well tolerated and appears to offer the advantage of rapid and smooth induction and emergence from general anesthesia.

[Usefulness of cholesterol solvents administered percutaneously in the non-surgical treatment of biliary lithiasis]. / Utilidad de los solventes de colesterol aplicados por vía percutánea en el tratamiento no quirúrgico de la litiasis biliar.

We present the current state of the art in the use of Methyl tertbutyl ether (MTBE) in dissolution of gallbladder cholesterol stones, as well as the use of another solvents in case of common bile duct stones. MTBE is useful, with few collateral effects and is safe but must be used cautiously by skilled and experimented personal; the cost of equipment is high; MTBE could not be used in common bile duct stones, monoctanoic acid is used instead but it needs continuous vigilance while infused. We do not recommend the use of others substances.

[Clinical trial of etophamide in the treatment of chronic intestinal amebiasis]. / Ensaio clínico com etofamida no tratamento da amebíase intestinal crônica.

The author present the results obtained in the treatment of 100 patients suffering chronic intestinal amebiasis, employing a new drug--Etophamide, in a dose of 1,0 g per day, for three consecutive days. The tolerance of a new antiamebic drug was excellent in all patients, and the parasitological cure rate obtained was 92%. The author concluded that the new derivate amebicide used in this research is very effective for treatment of intestinal amebiasis infections.

General anaesthesia with the E.M.O. apparatus using air

A simple method of anaesthesia is described using an economically priced Ether-Air apparatus - the E.M.O., O.I.B., and a Ruben valve in a non-return system. It is maintained that with this apparatus and the proper use of muscle relaxants, first class operating conditions may be achieved in the remotest parts of the world comparable to any other accepted technique utilizing more elaborate apparatus. Indeed, the diligent application of a simple well-learned method is much less like to lead to complications and difficulties, and has the advantage of consistent reliability. The E.M.O. portable unit admits of a flexibility which is denied conventional, far more expensive anaesthetic apparatus (AU)