The Effect of Alternating Current Iontophoresis on Rats with the Chronic Constriction Injury to the Infraorbital Nerve

This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI) to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI: n = 5), AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP: n = 5), AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP: n = 5), and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine: n = 5). In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI) cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus

Skin permeability methodologies for topical absorption prediction

Memòria presentada per Víctor Carrer Vives per optar al títol de doctor per la Universitat de Barcelona. Directores: Lluisa Coderch Negra i Cristina Alonso Merino. Tutora: Ana Cristina Calpena CampmanyUnderstanding of skin absorption processes is needed not only for assessment of the safety aspects of chemicals, other xenobiotics, or cosmetic formulations but also to determine drug release of substances to the different skin strata and further to systemic circulation. In the field of pharmaceutical sciences, drug delivery to the skin is gaining more and more interest, owing to the high acceptance by patients. In this regard, two different cases have to be distinguished: local delivery to selected skin layers (e.g., antimycotics) and systemic delivery (e.g., hormones). In the context of bioavailability assessment, knowledge on the absorption behavior of the active compound is essential. For ethical reasons, fundamental skin absorption data can normally not be obtained by conducting in vivo studies. Therefore, other techniques must be used to obtain the desired information. One option to obtain these data is the use of in vitro penetration and permeation models

Electroencephalographic and cardiovascular responses to castration in Bos indicus bull calves and the mitigating effects of lidocaine or meloxicam administration

Australian Bos indicus cattle are legally able to be castrated without anaesthesia or analgesia up to the age of 12 months. Castration surgery is known to cause pain to cattle, though a reliable and consistent assessment of pain must be first optimised before analgesic therapies can be tested for this procedure. Studies in conscious cattle have demonstrated the difficulty in isolating pain responses from the stress of handling and human contact. This study aimed to investigate electroencephalographic and cardiovascular responses indicative of nociception in Bos indicus bull calves undergoing surgical castration whilst under general anaesthesia. Further, the mitigating effects of administration of local anaesthetic or systemic meloxicam on these electroencephalographic and cardiovascular responses were investigated. A total of 36 six-to-eight month old Bos indicus bull calves were included in this prospective, randomised, experimental study. Animals were randomly allocated to three groups of twelve (groups L – 260 mg of 2% lidocaine subcutaneously and intratesticularly five minutes prior to castration, M - 0.5 mg kg-1 of meloxicam subcutaneously 30 minutes prior to castration and C – no preoperative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9-1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle incision, T1). HR and MAP were compared at ten-second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the electroencephalograph (Ptot) were analysed using area-under-the-curve comparing T1 to B. All electroencephalographic variables were significantly different between B and T1. No differences in F50 were found between groups during T1. F95 and Ptot were significantly different between group L and groups C and M during T1. There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20-50 second periods. This study is the first description of electroencephalographic and cardiovascular responses to castration in Bos indicus cattle, and the effect of two different analgesic strategies in reducing these responses. Administration of lidocaine prior to castration significantly attenuated the acute post-operative nociceptive response. In addition, the preoperative administration of meloxicam attenuated the cardiovascular, but not the electroencephalographic, responses to castration in the peracute period. These findings provide support for the preoperative administration of lidocaine and give impetus for further research into the peracute anti-nociceptive effects of meloxicam for castration in Bos indicus bull calves

Applications and Emerging Trends of Hyaluronic Acid in Tissue Engineering, as a Dermal Filler, and in Osteoarthritis Treatment

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine including scaffolding for tissue engineering, dermatological fillers, and viscosupplementation for osteoarthritis treatment. HA is available in most connective tissues in body fluids such as synovial fluid and the vitreous humor of the eye. HA is responsible for several structural properties of tissues as a component of extracellular matrix (ECM) and is involved in cellular signaling. Degradation of HA is a step-wise process that can occur via enzymatic or non-enzymatic reactions. A reduction in HA mass or molecular weight via degradation or slowing of synthesis affects physical and chemical properties such as tissue volume, viscosity, and elasticity. This review addresses the distribution, turnover, and tissue-specific properties of HA. This information is used as context for considering recent products and strategies for modifying the viscoelastic properties of HA in tissue engineering, as a dermal filler, and in osteoarthritis treatment

Resistance To Multi Organ Failure And Metabolic Alterations After Global Ischemia/Reperfusion In The Arctic Ground Squirrel

Thesis (Ph.D.) University of Alaska Fairbanks, 2013Cardiac arrest (CA) and hemorrhagic shock (HS) are two clinically relevant situations where the body undergoes global ischemia/reperfusion (I/R). Hibernating animals such as ground squirrels have been shown to be resistant to I/R injury in various tissues. The present study compared physiological and metabolic changes occurring during global I/R in an I/R-injury prone animal, the rat, to that of I/R injury resistant animals, arctic ground squirrels (AGS). We sought to determine if AGS are protected from multi organ failure after global I/R and if any protection is dependent upon their hibernation season or the ability to maintain a stable metabolic profile during I/R. For CA, rats and euthermic AGS were asphyxiated for 8 min, inducing CA. For HS, rats, euthermic AGS, and interbout arousal AGS were subject to HS by withdrawing blood to achieve a MAP of 35 mm Hg for 20 min before reperfusion. For both I/R models, the animals' temperature was maintained at 36.5-37.5�C. After reperfusion, animals were monitored for 3 hours (HS) or 7 days (CA), then tissues and blood were collected for histopathology, clinical chemistries, cytokine level analysis (HS only), and 1H-NMR metabolomics of hydrophobic and hydrophilic metabolites (HS only). For the HS studies, a group of rats and AGS were monitored for three days after HS to access survival and physiological impairment. Regardless of season AGS showed no physiological deficit 12 hours after HS or CA. Blood chemistries and circulating cytokine levels indicated liver damage and systemic inflammation in the rats while AGS showed no signs of organ damage or inflammation. In addition, rats had a shift in their hydrophilic metabolic fingerprint and alterations in several metabolite concentrations during HS-induced I/R, indicative of metabolic adjustments and organ damage. In contrast, AGS, regardless of season, were able to maintain a 1H-NMR metabolic profile with few changes in quantified metabolites during I/R. These data demonstrate that AGS are resistant to systemic inflammation and organ damage/failure after I/R and this resistance is not dependent on their ability to become hypothermic during insult but may stem from an intrinsic resistance to disruptions in their metabolic processes during I/R

Targeted topical delivery of peptides and small molecules to the skin

This PhD project demonstrates the importance of minimally invasive techniques such as microneedles and non-invasive techniques such as cell penetrating peptides and magnetophoresis for enhanced transdermal delivery. Skin penetration strategies studied, showed enhancement in delivery of peptides and small molecules ranging from a few percent to several fold and have tremendous potential for clinical therapy upon demonstration of safety and efficacy

Modulation of the Sodium/Potassium ATPase Function and Expression by Transcranial Direct Current Stimulation of the Right Sensorimotor Cortex in Mice

Direct current stimulation is used as a noninvasive therapeutic technique to enhance motor recovery following stroke, and to improve cognitive functions. This technique also showed promising results in the treatment of depression, schizophrenia, and multiple sclerosis. Transcranial direct current stimulation has been proven to cause a polarization (depolarization or hyperpolarization) of the target tissues depending on the polarity of the current and cell orientation. Because of the induced polarization, the spontaneous activity of the neurons is further affected. With exception to this electrophysiological effect, the overall biological mechanisms of transcranial direct current stimulation on the underlying tissues remain largely unknown. The present study aimed to reveal the effects of this technique on molecular targets that play a role in the generation and maintenance of cells’ membrane potentials. More specifically, this study focused on the sodium/potassium ATPase whose role in the generation of the membrane potential is essential. It also focused on other molecules that control the activity of the pump. Findings of this study revealed that cathode transcranial direct current stimulation increases the expression of alpha1 sodium/potassium ATPase protein and gene. The expression of beta 2 sodium/potassium ATPase was also increased following anode direct current stimulation. Similarly, the expression of alpha 1 sodium/potassium ATPase phospho-serine 943 and alpha 1 sodium/potassium ATPase phospho-serine 23 increased after anode transcranial direct stimulation. Taken together, these results showed that transcranial direct current stimulation influences the expression and regulation of the sodium/potassium ATPase

Chronobiology of Acid-Base Balance under General Anesthesia in Rat Model

The design and development of experimental, in vivo, chronobiological animal models may help reveal some of the relationships between circadian rhythms and biological functions. In vivo experiments require the use of appropriate anesthesia, which should be selected according to their particular effect on the organism. The aim of study was to review the status of acid-base balance and ion concentration in arterial blood under common used general anesthesias in experiments in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using 3- to 4-month-old pentobarbital(P)-, ketamine/xylazine(K/X)-, and zoletil(Z)-anesthetized female Wistar rats after a 4-week adaptation to an LD cycle (12 h light and 12 h dark). We concluded that P anesthesia disturbs LD dependence of acid-base balance compared to K/X and Z anesthesia, but LD differences in plasma ion concentrations are disturbed under all type of general anesthesia. P anesthesia is not the most appropriate type of anesthesia in rat chronobiological experiments. It eliminated LD differences and also produces a more acidic environment, more pronounced hypercapnia and hypoxia than K/X and Z anesthesias. This should be taken into account because the altered internal environment may affect the activity of systems whose functions are primarily dependent on acid-base balance