Inhibitory Effect of Gallium Nitrate against Staphylococcus aureus and Its Action on the Formation of Biofilms on Titanium Surfaces

Aims: This study aimed to investigate the effect of gallium nitrate [Ga(NO3)3], an inorganic antimicrobial agent, against the growth and biofilm formation of Staphylococcus aureus on the titanium surface. Study Design: This study is a laboratory investigation involving the determination of the inhibitory concentration (IC) of Ga(NO3) 3 against the planktonic strain of S. aureus and biofilm formation on titanium coupons. Place and Duration of Study: Sample: Center of Science and Technology for Sustainability (CCTS), Federal University of São Carlos, SP, Brazil, between March 2020 and March 2022. Methodology: The inhibitory concentration of gallium nitrate was determined in a 96-well microtiter plate in Muller Hinton broth. The potential of the antimicrobial agent to inhibit biofilm formation by S. aureus on titanium surfaces was evaluated by Scanning Electron Microscopy (SEM). The cytotoxicity potential of Ga(NO3)3 was determined on V79 cells. Results: The results showed that the susceptibility of gallium nitrate against S. aureus was 1.40 µM, while SEM images revealed that concentrations of 90 µM inhibited biofilm formation by S. aureus. Conclusion: This research has shown promising results regarding gallium nitrate's potential of inhibiting the growth of both planktonic and sessile S. aureus cells. In addition, coating titanium surfaces with Ga(NO3)3 would be an extra alternative to prevent implant-associated infections due to its non-toxicity to cells.

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Comparación de Algoritmos Lineales y no Lineales para la Detección del Desacoplamiento Cardiorrespiratorio en Ratas Endotoxémicas / Comparison of Linear and Nonlinear Algorithms for Detection of Cardiorespiratory Uncoupling in Endotoxemic Rats

Resumen En estudios previos se ha demostrado que la endotoxemia inducida por lipopolisacárido (LPS) produce un desacoplamiento cardiorrespiratorio (CRP) debido a los efectos fisiológicos de la inflamación sistémica. Adicionalmente se sabe que la oxitocina tiene efectos antiinflamatorios y propiedades cardioprotectoras; sin embargo, se desconoce si ésta modifica el acoplamiento CRP. El objetivo del presente estudio fue comparar diferentes métodos matemáticos lineales y no lineales para la detección del desacoplamiento cardiorrespiratorio entre series de tiempo cardiacas y respiratorias. Se estudiaron series de tiempo R-R obtenidas de electrocardiogramas de grupos de roedores macho a los cuales se les administró solución salina o vehículo (V); lipopolisacárido (LPS); oxitocina (O) y LPS + oxitocina (LPS+Ox). Las series R-R y respiratorias derivadas del electrocardiograma (EDR) se analizaron en conjunto para cuantificar su grado de acoplamiento a través de las técnicas de correlación cruzada; entropía muestral cruzada; entropía condicional; información mutua; e información mutua de Rényi para los cuatro grupos. Se observó que la oxitocina no parece favorecer el acoplamiento CRP durante la endotoxemia inducida por LPS. Finalmente, se encontró que la entropía muestral cruzada y la entropía condicional presentaron las mayores diferencias estadísticas para identificar el desacoplamiento CRP producido por el LPS.

Abstract Previous studies have shown that LPS-induced endotoxemia causes a cardiorespiratory (CRP) uncoupling owing to the physiological effects of systemic inflammation. Also, it is known that oxytocin has anti-inflammatory effects and cardioprotective properties; however, it is unknown whether it can modify the CRP coupling. This study aimed to compare different linear and nonlinear mathematics methods for the detection of cardiorespiratory uncoupling between cardiac and respiratory time series. The R-R time series of electrocardiograms of male rodents that were administered with saline solution (V); lipopolysaccharide (LPS); oxytocin (O) and LPS + oxytocin (LPS + Ox) were studied. We tested the R-R and respiratory series derived from the electrocardiogram (EDR) for the four groups to quantify the degree of coupling with cross-correlation; cross sample entropy; conditional entropy; mutual information; and Rényi's mutual information. We found that oxytocin does not seem to favor the CRP coupling during endotoxemia induced by LPS. Finally, we observed that the cross-sample entropy and the conditional entropy presented the highest statistical differences to identify the CRP uncoupling produced by LPS.

Efeitos de um manual de instrução sobre o repertório de comportamentos de acompanhantes de crianças com câncer / Effects of an instruction manual on behavioral repertoires of caregivers of children with cancer

Este estudo teve por objetivo analisar os efeitos, em curto e em médio prazo, de um manual de instruções sobre comportamentos observados em acompanhantes e crianças com câncer durante realização de punção venosa em ambulatório.Participaram doze cuidadoras (idade média de 24 anos) de crianças cuja maioria (n= 8) tinha diagnóstico de leucemia. A coleta consistiu emuma observação antes da aplicação do manual e duas após o manual (efeito em curto e médio prazo). Observou-se diminuição significativa na taxa do comportamento de Desviar atenção do procedimento e uma tendência ao aumento na taxa do comportamento de Demonstrar carinho.Discute-se a efetividade do uso de manuais sobre mudanças comportamentais na área da saúde

The aim of this study was to assess the short and mid-term effects of an instruction manual on the observable behaviors of caregivers of children with cancer during venipuncture in an outpatient setting. Twelve caregivers (mean age of 24 years old) participated while most children (n = 8) had been diagnosed with leukemia. Data collection consisted in one observation before, and two others after the manual presentation (short and mid - term effect). A significant decrease was observed in the rate of behavior of attention distraction from the procedure, and a tendency to an increase in showing love and affection. We discuss the effectiveness of the use of manuals on behavior changes in the are of health

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E2 (PGE2, 2 μg/paw) in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 μg/paw) and AM-630 (100 μg/paw) were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g), 20 μg diclofenac (mean = 4.825 ± 3.850 g) and 40 μg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and indomethacin.

Participation of endogenous opioids in the antinociception induced by resistance exercise in rats

Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group): untrained rats (control group); an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group), and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group). The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction) was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37 percent, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15 percent after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.

Opioidergic orofacial antinociception induced by electroacupuncture at acupoint St36

The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 ± 0.1; 30 Hz: 1.8 ± 0.1; 100 Hz: 1.7 ± 0.1 vs 1.4 ± 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 ± 0.2 vs 1.0 ± 0.1) was used, and not with 5 or 30 Hz (1.2 ± 0.2 and 0.7 ± 0.1 vs 1.0 ± 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 ± 0.2 and 1.7 ± 0.2 vs 3.0 ± 0.1).

Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats

We examined the effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP), and cesium on the ability of fentanyl, a clinically used selective æ-opioid receptor agonist, to promote peripheral antinociception. Antinociception was measured by the paw pressure test in male Wistar rats weighing 180-250 g (N = 5 animals per group). Carrageenan (250 æg/paw) decreased the threshold of responsiveness to noxious pressure (delta = 188.1 ± 5.3 g). This mechanical hyperalgesia was reduced by fentanyl (0.5, 1.5 and 3 æg/paw) in a peripherally mediated and dose-dependent fashion (17.3, 45.3 and 62.6 percent, respectively). The selective blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 æg/paw) and tolbutamide (80, 160 and 240 æg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 æg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 æg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 æg/paw), or the non-specific K+ channel blocker TEA (150 æg/paw), 4-AP (50 æg/paw), and cesium (250 æg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral æ-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.

Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats

Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20 percent (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74 percent (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11) and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11) models of epilepsy. Naloxone (5 mg/kg, sc) significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test), suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc) was demonstrable. The acute (120 mg/kg, ip) and chronic (25 mg/kg, ip, twice a day/4 days) administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip) used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures

Tratamento cirúrgico da ptose palpebral adquirida (linfocitoma cútis) / Surgical treatment of acquired palpebral ptosis (lymphocitoma cutis)

Os autores descrevem um caso clínico de ptose palpebral causada por uma patologia rara, o linfocitoma cútis. A paciente apresentava o quadro clínico do linfocitoma cútis em sua forma disseminada, com sintomatologia visual causada por nódulos palpebrais. A conduta cirúrgica realizada foi a ressecçäo dos nódulos palpebrais por meio de incisÒo de blefaroplastia, e o exame histológico confirmou o diagnóstico de linfocitoma cútis. O tratamento cirúrgico realizado foi eficiente para a melhora funcional das pálpebras.

Abdominoplasty: a personal approach to the aponeurotic muscle system

A new approach to the correction of distasis and flaccidness of the aponeurotic muscle system of the abdominal wall is presented, leading to the obtention of better results.

Disseminated lymphocytoma cutis

Lymphocytoma cutis is rare pathology affecting mainly the head and neck. Because of its rarity, the authors describe a clinical case in which the face was severely affected, as well as the histological examination and surgical management for functional eyelid improvement.