Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle

PURPOSE. Surgical recession of an extraocular muscle (EOM) posterior to its original insertion is a common form of strabismus surgery, weakening the rotational force exerted by the muscle on the globe and improving eye alignment. The purpose of this study was to assess myosin heavy chain (MyHC) isoform expression and satellite cell activity as defined by Pax7 expression in recessed EOMs of adult rabbits compared with that in muscles tenotomized but not recessed and with that in normal control muscles. METHODS. The scleral insertion of the superior rectus muscle was detached and sutured either 7 mm posterior to its original insertion site (recession surgery) or at the same site (tenotomy). One day before euthanatization, the rabbits received bromodeoxyuridine (BrdU) injections. After 7 and 14 days, selected EOMs from both orbits were examined for changes in fast, slow, neonatal, and developmental MyHC isoform expression, Pax7 expression, and BrdU incorporation. RESULTS. Recession and tenotomy surgery resulted in similar changes in the surgical EOMs. These included a decreased proportion of fast MyHC myofibers, an increased proportion of slow MyHC myofibers, and increased BrdU-positive satellite cells. Similar changes were seen in the non-operated contralateral superior rectus muscles. The ipsilateral inferior rectus showed reciprocal changes to the surgical superior rectus muscles. CONCLUSIONS. The EOMs are extremely adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression. These adaptive responses could be manipulated to improve surgical success rates. (Invest Ophthalmol Vis Sci. 2010;51:5646-5656) DOI:10.1167/iovs.10-5523

Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy

Objective-To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or mandibulectomy. Animals-42 dogs with oral neoplasms. Procedures-30 minutes before the end of surgery, dogs received SC injections of tramadol (2 mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol + ketoprofen, or codeine + ketoprofen (at the aforementioned dosages). Physiologic variables, analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24 hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations were measured 1, 3, 5, and 24 hours after administration of analgesics. Results-All treatments provided adequate postoperative analgesia. Significant increases in mean +/- SD blood glucose concentrations were detected in dogs receiving tramadol (96 +/- 14 mg/dL), codeine (120 +/- 66 mg/dL and 96 +/- 21 mg/dL), ketoprofen (105 +/- 22 mg/dL), and codeine + ketoprofen (104 +/- 16 mg/dL) at 5, 1 and 3, 5, and 3 hours after analgesic administration, respectively, compared with preoperative (baseline) values. There were no significant changes in physiologic variables, serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered codeine + ketoprofen had light but significant sedation at 4, 5, and 24 hours. Conclusions and Clinical Relevance-Opioids alone or in combination with an NSAID promoted analgesia without adverse effects during the 24-hour postoperative period in dogs undergoing maxillectomy or mandibulectomy for removal of oral neoplasms. (Am J Vet Res 2010;71:1019-1026)

Evaluation of Efficacy and Safety of Zinc Gluconate Associated with Dimethyl Sulphoxide for Sexually Mature Canine Males Chemical Neutering

Contents The aim of this research was to evaluate the efficacy of zinc gluconate associated with dimethyl sulphoxide (DMSO) for chemical neutering in canine males. Fifteen sexually mature male dogs were divided in two groups, named control and treated. An injection was administered to both testicles, at a concentration of 26.2 mg zinc gluconate per ml and 0.5% DMSO in the treated group (11 dogs). The control group was given injections of saline solution (four dogs). Clinical examination and blood collection for a haemogram were done both before and after drug injection. There were 12 spermograms performed to analyse sperm motility, sperm vigour, ejaculate volume, testicle size, pathology and sperm concentrations. Libido was also measured. An ultrasound examination and histopathology were performed at the end of the experiment. Dogs` libido after chemical injection was reduced by over 50%. The spermogram analysis showed final mean results of 14.54% for sperm motility, 0.72 of sperm vigour and 37 150 per million spermatozoa per millilitre, values considered below the necessary levels at which fertilization can occur. Ultrasound and histopathology analyses of testicles for the treated group revealed more intense injuries when compared with the control group, with compromised testicular parenchyma and a decrease of germ cell number leading to total atrophy, indicating that the treatment reduced the fertilizing potential of male dogs, promoting a possible subfertile status.

Reproductive toxic effects of Tityus serrulatus scorpion venom in rats

Tityus serrulatus is the most venomous scorpion in Brazil. Little is known about the effect of maternal exposure to the venom on fetal development. We investigated the effect of low to moderate doses of the venom (0.3 or 1.0 mg/kg s.c. on either day 5 or day 10 of gestation) on pregnant rats and on their offspring. For dams, we observed their body weight gain and reproductive parameters. For the offspring, we observed their body weight and weight of internal organs and the number of live and dead fetuses, and we investigated whether the venom caused external, visceral, skeletal or histopathological alterations in the offspring. The offspring were examined on gestational day 21. Injection of the venom on gestational day 5 did not change the reproductive parameters of the dams, their weight or fetuses` weight. Rats that received the high dose of the venom (1.0 mg/kg) on gestational day 10 had heavier placentas and heavier fetuses with heavier lungs. Injections on day 10 of gestation did not alter the reproductive parameters of the dams nor their weight gain at either dose. The venom did not cause malformations of the fetal skeleton or viscera and did not delay fetal development with either dose. In conclusion, subcutaneous administration of 0.3 or 1.0 mg/kg T. serrulatus venom to pregnant Wistar rats at either day 5 or day 10 of gestation did not cause maternal or clear fetal toxicity. Subtle increases in placental weight and fetal body and lung weights observed following treatment with 1.0 mg/kg on day 10 of gestation were not associated with histopathological findings. Whether these observations represent a reaction to treatment and, if so, the underlying mechanisms and their toxicological impact remain to be examined further in future studies. (C) 2008 Elsevier Inc. All rights reserved.

A new presynchronization system (Double-Ovsynch) increases fertility at first postpartum timed AI in lactating dairy cows

This study evaluated a novel presynchronization method, using Ovsynch prior to the Ovsynch-timed AI protocol (Double-Ovsynch) compared to Presynch-Ovsynch. Lactating Holstein (n = 337) cows, were assigned to two treatment groups: (1) Presynch (n = 180), two injections of PGF 14 d apart, followed by the Ovsynch-timed AI protocol 12 d later; (2) Double-Ovsynch (n = 157), received GnRH, PGF 7 d later, and GnRH 3 d later, followed by the Ovsynch-timed AI protocol 7 d later. All cows received the same Ovsynch-timed AI protocol: GnRH (G1) at 68 +/- 3 DIM (mean +/- SEM), PGF 7 d later, GnRH (G2) 56 h after PGF, and AI 16 to 20 h later. Pregnancy was diagnosed 39-45 d after timed AI. Double-Ovsynch increased the pregnancies per AI (P/AI) compared to Presynch-Ovsynch (49.7% vs 41.7%, P = 0.03). Surprisingly, Double-Ovsynch increased P/AI only in primiparous (65.2% vs 45.2%; P = 0.02) and not multiparous (37.5% vs 39.3%) cows. In a subset of 87 cows, ovarian ultrasonography and progesterone (P4) measurements were performed at G1 and 7 d later. Double-Ovsynch decreased the percentage of cows with low P4 (<1 ng/mL) at G1 (9.4% vs 33.3%) and increased the percentage of cows with high P4 (>= 3 ng/mL) at PGF (78.1% vs 52.3%). Thus, presynchronization of cows with Double-Ovsynch increased fertility in primiparous cows compared to a standard Presynch protocol, perhaps due to induction of ovulation in non-cycling cows and improved synchronization of cycling cows. Future studies are needed, with a larger number of cows, to further test the hypothesis of higher fertility with Double-Ovsynch, and to elucidate the physiological mechanisms that underlie apparent changes in fertility with this protocol. (C) 2008 Elsevier Inc. All rights reserved.

Evaluation of the buccal vestibule-palatal diffusion of 4% articaine hydrochloride in impacted maxillary third molar extractions

Aims: The aim of this study was to evaluate the vestibular-palatal diffusion of 4% articaine with epinephrine 1: 100,000 and 1: 200,000, in impacted maxillary third molar extractions, without palatal injection. Materials and Method: Two hundred teeth were selected from patients age 15 to 46. Patients were divided into 4 groups: 1A, were anesthetized with 4% articaine 1: 100,000 and the surgery was initiated 5 minutes following anesthesia. 1B, used 4% articaine 1: 100,000 but the surgery was started 10 minutes after anesthesia. 2A, used 4% articaine 1: 200,000 the surgery was started 5 minutes after. 2B, used 4% articaine 1: 200,000 but 10 minutes was allowed for anesthetic diffusion before the initiation of in groups (50 extractions each) only buccal vestibule anesthesia was initially administered (i.e. no palatal injections were used). Results: The rate of sufficient vestibule-palatal diffusion, as determined by the lack of necessity of supplemental palatal anesthesia, was: 1A(84%), 1B(98%), 2A(78%), 2B(82%). Chi-square (X2) and residual analyses showed that a higher vestibule-palatal diffusion was obtained using 4% articaine 1: 100,000 with a period of 10 minutes (p<0.05). Conclusions: Most of the extractions could be performed only with vestibule anesthesia. However, vasoconstrictor concentration and the time interval between administration of the anesthetic and initiation of surgery did influence buccal vestibule-palatal diffusion of 4% articaine in the extraction models used.

Role of the spinal cord heme oxygenase-carbon monoxide-cGMP pathway in the nociceptive response of rats

The aim of the present study was to investigate the role of the spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase (sGC)-cGMP pathway in nociceptive response of rats to the formalin experimental nociceptive model. Animals were handled and adapted to the experimental environment for a few days before the formalin test was applied. For the formalin test 50 mu l of a 1% formalin solution was injected subcutaneously in the dorsal surface of the right hind paw. Following injections, animals were observed for I h and flinching behavior was measured as the nociceptive response. Thirty min before the test, rats were pretreated with intrathecal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control animals were treated with vehicles. We observed a significant increase in nociceptive response of rats treated with ZnDPBG, and a drastic reduction of flinching nociceptive behavioral response in the heme-lysinate treated animals. Furthermore, the HO pathway seems to act via cGMP, since methylene blue (a sGC inhibitor) prevented the reduction of flinching nociceptive behavioral response caused by heme-lysinate. These findings strongly indicate that the HO pathway plays a spinal antinociceptive role during the formalin test, acting via cGMP. (C) 2007 Elsevier B.V. All rights reserved.

Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis

In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric Oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24 h after the surgeries and the brains were removed and processed for Fos immunocytochemistry We observed an increase (P < 0.001) in c-fos expression 6 h after CLP in the area postrema (AP), nucleus of he tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24 h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P < 0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6 h after CLR but showed an opposite effect at 24 h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24 h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress. we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201 +/- 5 vs. 163 +/- 7 mm Hg in diabetic rats untreated and treated with lercaniclipine, respectively; P < 0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P < 0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P < 0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P < 0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2MMP-2 expression. (C) 2008 Published by Elsevier B.V.

Role of central nitric oxide in behavioral thermoregulation of toads during hypoxia

Nitric oxide (NO) is thought to play a key role in the development of hypoxia-induced anapyrexia in mammals, acting on the preoptic region of the anterior hypothalamus to activate autonomic heat loss responses. Regarding behavioral thermoregulation, no data exists for NO modulation/mediation of thermoregulatory behavior changes during hypoxia. Therefore, we tested the hypothesis that NO is involved in the preferred body temperature (Tb) reduction in the hypoxic toad Chaunus schneideri (formerly Bufo paracnemis), a primarily behavioral thermoregulator. Toads equipped with a temperature probe were placed in a thermal gradient chamber, and preferred Tb was monitored continuously. We analyzed the effect of intracerebroventricular injections of the nonselective NO synthase inhibitor L-NMMA (200, 400 and 800 microg per animal) or mock cerebrospinal fluid (mCSF, vehicle) on the preferred Tb of toads. No significant difference in preferred Tb was observed after L-NMMA treatments. Another group of toads treated with 2 mg kg(-1) (400 microg per animal) of L-NMMA or mCSF was submitted to hypoxia (3% inspired 02) for 8 h. The vehicle group showed a reduction of preferred Tb, a response that was inhibited by L-NMMA. A 3rd group of hypoxic animals was injected with Ringer or L-NMMA (2 mg kg(-1)) into the lymph sac and both treatments induced no change in the anapyretic response to hypoxia. These results indicate that NO acting on the central nervous system has an excitatory role for the development of hypoxia-induced anapyrexia in toads. (C) 2008 Elsevier Inc. All rights reserved.

The effects of information request ambiguity and construct incongruence on query development

This paper examines the effects of information request ambiguity and construct incongruence on end user's ability to develop SQL queries with an interactive relational database query language. In this experiment, ambiguity in information requests adversely affected accuracy and efficiency. Incongruities among the information request, the query syntax, and the data representation adversely affected accuracy, efficiency, and confidence. The results for ambiguity suggest that organizations might elicit better query development if end users were sensitized to the nature of ambiguities that could arise in their business contexts. End users could translate natural language queries into pseudo-SQL that could be examined for precision before the queries were developed. The results for incongruence suggest that better query development might ensue if semantic distances could be reduced by giving users data representations and database views that maximize construct congruence for the kinds of queries in typical domains. (C) 2001 Elsevier Science B.V. All rights reserved.

Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor

Hypothalamic-pituitary-adrenal axis activation is a hallmark of the stress response. In the case of physical stressors, there is considerable evidence that medullary catecholamine neurones are critical to the activation of the paraventricular nucleus corticotropin-releasing factor cells that constitute the apex of the hypothalamic-pituitary-adrenal axis. In contrast, it has been thought that hypothalamic-pituitary-adrenal axis responses to emotional stressors do not involve brainstem neurones. To investigate this issue we have mapped patterns of restraint-induced neuronal c fos expression in intact animals and in animals prepared with either paraventricular nucleus-directed injections of a retrograde tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint-induced patterns of neuronal activation within the medulla of intact animals were very similar to those previously reported in response to physical stressors, including the fact that most stressor-responsive, paraventricular nucleus-projecting cells were certainly catecholaminergic and probably noradrenergic. Despite this, the destruction of paraventricular nucleus catecholamine terminals with 6-hydroxydopamine did not alter corticotropin-releasing factor cell responses to restraint. However, animals with ibotenic acid lesions encompassing either the A1 or A2 noradrenergic cell groups displayed significantly suppressed corticotropin-releasing factor cell responses to restraint. Notably, these medullary lesions also suppressed neuronal responses in the medial amygdala, an area that is now considered critical to hypothalamic-pituitary-adrenal axis responses to emotional stressors and that is also known to display a significant increase in noradrenaline turnover during restraint. We conclude that medullary neurones influence corticotropin-releasing factor cell responses to emotional stressors via a multisynaptic pathway that may involve a noradrenergic input to the medial amygdala. These results overturn the idea that hypothalamic-pituitary-adrenal axis response to emotional stressors can occur independently of the brainstem. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

Somatotopic organization and cortical projections of the ventrobasal complex of the flying fox: an "inverted" wing representation in the thalamus

The present study investigates the somatotopic representation in the somatosensory thalamus of a megachiropteran bat. Using standard microelectrode mapping techniques, representational maps were generated for the ventrobasal (Vb) and posterior (Po) thalamic complexes of the Grey-headed flying fox. Anatomical tracing from neocortical injections provided additional data confirming the somatotopy found physiologically. A full representation of the body surface innervated by the trigeminal and spinal nerves was found. However, in contrast with other mammals, the representations of the forelimb and adjacent thoracic trunk within the thalamus were inverted. This means that the distal portions of the wing membrane and the tips of the digits were represented dorsally in Vb, and the thoracic trunk was represented ventrally In Po the digit tips were represented in the ventral most portion and the thoracic trunk in the dorsal portion of the nucleus. These results are discussed in relation to similarities of megachiropteran somatosensory thalamic nuclei to those of other mammalian species and in relation to the formation of thalamic somatotopic maps and fiber sorting.

Immune response to Bacteroides forsythus in a murine model

A murine skin abscess model was used to study the immune response to an acute infection with Bacteroides forsythus. BALB/c mice were given subcutaneous injections of either viable or heat-killed B. forsythus, while a third sham-immunized control group received phosphate-buffered saline. Weights and lesion sizes were measured. Blood was collected from the heart and specific antibodies to B. forsythus measured by an ELISA. Swabs taken from the lesions and also from pooled blood were cultured anaerobically for viable B. forsythus. Viable B. forsythus-induced lesions reached maximum size at day 7. B. forsythus cells were recovered from lesions up to day 4 although none were cultured from blood samples. Heat-killed bacteria induced much smaller lesions. Serum antibody levels increased during the 9-day study period, being significantly higher in mice injected with viable compared with heat-killed B. forsythus. Antibody levels in sham control mice were significantly lower than those seen in the other two groups. These results showed that a subcutaneous injection of viable cells of B. forsythus elicited a pronounced abscess formation and induce higher levels of specific antibodies compared with that produced by an injection of dead bacteria. This suggests that, as with other periodontopathic organisms, this mouse model can be used to study the immune response to B. forsythus.

Hydromorphone-3-glucuronide - A more potent neuro-excitant than its structural analogue, morphine-3-glucuronide

In humans, hydromorphone (HMOR) is metabolised principally by conjugation with glucuronic acid to form hydromorphone-3-glucuronide (H3G), a close structural analogue of morphine-3-glucuronide (M3G), the major metabolite of morphine. In a previous study we described the biochemical synthesis of H3G together with a preliminary evaluation of its pharmacology which revealed that it is a neuro-excitant in rats in a manner analogous to M3G. Thus the aims of the current study were to quantify the neuro-excitatory behaviours evoked by intracerebroventricular (icv) H3G in the rat and to define its potency relative to M3G. Groups of adult male Sprague-Dawley rats received icy injections (1 muL) of H3G (1 - 3 mug), M3G (2 - 7 mug) or vehicle via a stainless steel guide cannula that had been implanted stereotaxically seven days prior to drug administration. Behavioural excitation was monitored by scoring fifteen different behaviours (myoclonic jerks, chewing, wet-dog-shakes, rearing, tonic-clonic-convulsions, explosive motor behaviour, grooming, exploring, general activity, eating, staring, ataxia, righting reflex, body posture, touch evoked agitation) immediately prior to icy injection and at the following post-dosing times: 5, 15, 25, 35, 50, 65 and 80 min. H3G produced dose-dependent behavioural excitation in a manner analogous to that reported previously for M3G by our laboratory and reproduced herein. H3G was found to be approximately 2.5-fold more potent than M3G, such that the mean (+/- S.D.) ED50 values were 2.3 (+/- 0.1) mug and 6.1 (+/- 0.6) mug respectively. Thus, our data clearly imply that if H3G crosses the BBB with equivalent efficiency to M3G, then the myoclonus, allodynia and seizures observed in some patients dosed chronically with large systemic doses of HMOR, are almost certainly due to the accumulation of sufficient H3G in the central nervous system, to evoke behavioural excitation. (C) 2001 Elsevier Science Inc. All rights reserved.