Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10), or control group - we studied the feasibility of muscle contractility; group II (n=10), in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05). In group II, a significant depression occurred in all periods, except between the last 2 periods (p<0.05). Comparing groups I and II only in period 1, which was a standard period for both groups, we found no significant difference (p>0.05). CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

Effect of escitalopram on the processing of emotional faces

Serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. The aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. Twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. A single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. Participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10% steps. Escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. No drug effect on subjective measures was detected. These results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. Further studies including female volunteers are needed.

Effect of alcohol on the rat juxtaprostatic pelvic ganglia and gonads.

In the present paper, it was investigated the aspect of the intrapelvic autonomic neuronal system (juxtaprostatic ganglion) and gonads of rats submitted to a experimental alcoholism. The animals which had water substituted for 35% sugar cane spirit for 30 d, presented testicular lesions as well as numeric and degenerative alterations in the juxtaprostatic pelvic ganglia neurons.

Effects of antithyroid drug on the rectal temperature and metabolic parameters of ducks (Cairina moschata).

The effect of propylthiouracil oral treatment (400 mg/day per bird for 20 days) on body and thyroid weight, rectal temperature and plasma metabolic parameters of ducks (Cairina moschata) was determined. Propylthiouracil treatment produced a reduction (P less than .01) in body weight and an increase (P less than .01) in thyroid weight. The antithyroid drug also produced a decrease in rectal temperature starting from the 15th day of treatment, but did not significantly change blood glucose. Plasma free fatty acids and cholesterol concentrations progressively increased from the 5th and 10th day, respectively, in treated animals.

The effect of bovine interferon-alpha I1 on pregnancy rate in heifers.

Bovine interferon-alpha I1 (bIFN-alpha) may be useful for enhancing fertility in sheep and cattle because it has extensive sequence homology with ovine and bovine trophoblast protein-1 and, like those proteins, extends corpus luteum lifespan. To test the effectiveness of bIFN-alpha to enhance fertility, several experiments were performed in which inseminated heifers were given i.m. injections of bIFN-alpha approximately at the time of embryo-mediated signals that result in maintenance of the corpus luteum. In Exp. 1, heifers given 20 mg of bIFN-alpha daily from d 14 to 17 tended (P less than .07) to have lower pregnancy rates at d 110 to 112 of gestation (36/75; 48% vs 43/72; 60%). Similar results were obtained in Exp. 2 when heifers received a single injection of 40 mg of bIFN-alpha or placebo at d 13 after estrus; pregnancy rates at d 42 were 39/104 (38%) for bIFN-alpha and 47/98 (48%) for placebo. In Exp. 3, heifers were given gradually increasing doses of bIFN-alpha or placebo from d 11 to 19, because such a regimen had been shown to reduce the number of heifers experiencing hyperthermia after bIFN-alpha injection. Pregnancy rates were 42/95 (44%) for bIFN-alpha and 62/111 (56%) for placebo. Across all three experiments, pregnancy rates were lower (P less than .01) for heifers treated with bIFN-alpha (117/274; 43%) than for heifers treated with placebo (152/281; 54%). In conclusion, these results demonstrate that, under the administration systems used, bIFN-alpha does not increase pregnancy rate, but rather tends to reduce it.

Protective effect of nickel chloride on superoxide damage: enhancement of CuZn superoxide dismutase affinity to the oxygen free radical.

The effect of nickel from soluble NiCl2 on Cu-Zn superoxide dismutase (SOD) activity, as well as on rate of nitro blue tetrazolium reduction, was studied in vitro since lipid peroxidation has been implicated in cell damage by nickel insoluble compounds, whose toxicity and carcinogenicity are well established. The physical and chemical nature of nickel compounds is one of the key determinations of its toxicity. Soluble nickel freely enter cells, but is just as readily excreted reducing the opportunity for production of lipid damage. Nickel from NiCl2 strongly activated SOD activity. In vitro addition of nickel chloride to a crude lung preparation altered the KM for SOD without changing the Vmax. Nickel chloride produced increased enzyme affinity to the substrate, because decreased (O2-) concentration that yields half-maximal velocity. The combination of nickel and SOD may contribute to stabilization of the particular conformation of SOD responsible for maximal catalytically activity.

Topical effect of propolis in the repair of sulcoplasties by the modified Kazanjian technique. Cytological and clinical evaluation.

A study was conducted to analyze the effects of propolis mouth rinse on the repair of surgical wounds after sulcoplasty by the modified Kazanjian technique. Twenty-seven patients who underwent sulcoplasty were divided into three groups: C1--patients who did not use the mouth rinse C2--patients who used a mouth rinse containing 5% aqueous alcohol T--patients who used a mouth rinse containing 5% propolis in aqueous alcohol solution. The patients returned 7, 14, 30, and 45 days after surgery for cytological and clinical evaluation. It was concluded that: 1) the mouth rinse containing propolis in aqueous alcohol solution aids repair of intra-buccal surgical wounds and exerts a small pain-killing and anti-inflammatory effect; 2) the vehicle employed has a minor irritant effect on intra-buccal surgical wounds; 3) exfoliative cytology allows epithelization of intrabuccal surgical wounds.

Effect of nicotinic stimulation of the amygdaloid complex on water and sodium chloride intake

We studied the nicotine stimulation of the amygdaloid complex (AMG) on sodium and water intake in satiated and water-deprived rats. Nicotine produced no change in sodium or water intake in satiated animals when injected directly into the AMG. In water-deprived animals, nicotine injected into the AMG (basolateral nuclei) only blocked sodium chloride intake. We have previously demontrated that carbachol inhibits water and sodium intake in both satiated and water-deprived animals injected into the AMG. Injection of hexamethonium into the AMG totally blocked water intake in satiated and water-deprived animals. Hexamethonium injected into the AMG prior to nicotine produced no change in sodium intake. Thus, the present data suggest that sodium and water intake are mediated by a specific population of cholinoceptive neurons in the amygdaloid complex.

Long-term effect of prolactin treatment on glucose-induced insulin secretion in cultured neonatal rat islets

Insulin secretion and 45SCa2+ uptake and efflux were studied in neonatal rat islets maintained in culture for 7 or 19 days in the absence or presence of prolactin (PRL). Insulin secretion in response to glucose (G), leucine (Leu), arginine (Arg) and carbachol (Cch) was augmented after 7 and 19 days in culture, compared to basal secretion (G 2.8 mM), in both PRL- treated and control islets. However, the increase in insulin secretion induced by the above secretagogues was higher in islets cultured in the presence of PRL for 19 days. In PRL-treated islets, the 45Ca2+ content after a 5 min incubation in the presence of G, Leu, Arg and Cch was significantly higher than the control only in islets cultured for 19 days. Except with Arg, the 45Ca2+ uptake in PRL-treated islets after a 90 min incubation was also significantly higher than the control only in islets cultured for 19 days. Finally, Leu-induced alterations in the 45Ca2+ efflux were higher in PRL-treated than in control islets cultured for 7 or 19 days. In the absence of external Ca2+, the reduction in 45Ca2+ efflux induced by glucose was also significantly higher in PRL-treated than in control islets. This effect was slightly potentiated after 19 days in culture. These data further support the hypothesis that PRL treatment enhances maturation of the secretory mechanism in neonatal islets. This effect can be potentiated even more if the treatment is prolonged.

Effect of α-tocopherol, taurine and selenium on the attenuation of ischemia/reperfusion injury of splanchnic organs

Background: Splanchnic artery occlusion shock is caused by increased capillary permeability and cellular injury precipitated by oxygen derived free radicals following ischemia and reperfusion of splanchnic organs. The purpose of this study was to assess the role of several well-known oxygen- derived free radical scavengers in ameliorating or preventing this syndrome. Study design: Anesthetized rats were subjected to periods of occlusion of the visceral arteries and reperfusion. Tocopherol, taurine, selenium or a 'cocktail' of these three agents was injected subcutaneously for 4 consecutive days prior to operation. Mean arterial blood pressure was measured throughout the experimental period. Fluorometry and technetium-99m pyrophosphate counting of the visceral organs were performed as well as a histologic grading system for intestinal viability. Results: Final mean arterial blood pressure associated with the 'cocktail' and selenium groups was 79.1 ± 27.4 mmHg and 83.6 ± 17.8 mmHg, respectively. These values were significantly higher than the control group, 40.8 ± 11.4 mmHg (P < 0.05). Similar patterns of the benefit of selenium in contrast with the other groups were obtained with fluorescein perfusion, radioisotopic activity and histologic analysis. Conclusion: Pretreatment with selenium of splanchnic ischemia and reperfusion in the rat improves mean arterial blood pressure and microcirculatory visceral perfusion. Further analysis of the precise protective mechanism of selenium for reperfusion injury will enable visceral organs to withstand the consequences of increased capillary leakage and oxidant injury.

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Effect of NωNLA or dexamethasone on vascular hyporeactivity induced by E. coli endotoxin in sham and adrenalectomized rats

Induction of iNOS by bacterial products is considered to be part of the defense mechanism against infection. However, it has been suggested that the bacterial-induced NO-overproduction may be involved in the vascular hyporeactivity and in septic shock. It is well known that glucocorticoids prevent the induction of iNOS by Etx in rats. In the present study, dexamethasone diminished but not abolished Etx-induced vascular hyporeactivity in rats. Our results showed that the inhibition of iNOS protects sham rats against the lethal shock produced by Etx, but, in Adx rats, the NωNLA, an iNOS inhibitor, did not reduce Etx-induced mortality. Interestingly, the lack of glucocorticoid impaired the protective effect of NωNLA against Etx-induced hyporeactivity and shock in rats. A conceivable pharmacological approach to protect tissues against deleterious effect of excessive NO production includes inhibition of the iNOS, because the absence of glucocorticoid may increase the iNOS gene expression, with NO-overproduction induced by Etx, suggesting that the glucocorticoids might be of therapeutic value for the treatment of hyporeactivity and shock triggered by sepsis.

Effect of isotretinoin on tooth germ and palate development in mouse embryos.

Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors. This study compares the tooth germs of the first maxillary and mandibular molars of fetal mice submitted to isotretinoin during organogenesis. Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated. After standard laboratory procedures, 6-micron thick serial slices were stained with hematoxylin and eosin for optical microscopy examination. The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.