Curcumin and its combination with a reduced dose of rosuvastatin: A promising therapy for chronic kidney disease and associated dyslipidemia in rat animal models.

The objective of this study was to confirm the effects of curcumin and to investigate the effects of its combination with a reduced dose of rosuvastatin in an adenine-induced model of chronic kidney disease (CKD) and associated dyslipidemia in rats. Renal function and morphology, as well as lipid status, were assessed using laboratory parameters and histopathological analysis. Male Wistar rats (n=36) randomly divided into six groups, were treated for 24 days: normal control (standard diet), CKD control (adenine diet, 0.75% w/w adenine-supplemented diet), curcumin (100 mg/kg/day + adenine diet), rosuvastatin minimal therapeutic dose (MTD) (5 mg/day + adenine diet), rosuvastatin reduced dose (RD, 25% of rosuvastatin MTD + adenine diet), and rosuvastatin RD + curcumin (25% of rosuvastatin MTD + curcumin 100 mg/kg/day + adenine diet) group. While rosuvastatin alone showed only antilipemic action, both curcumin alone and its combination with a reduced dose of rosuvastatin showed better renal protection with lower serum creatinine levels and milder renal morphological alterations, as well as better antilipemic action with lower levels of triglycerides, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterols compared with the levels in CKD control rats. Treatment with curcumin alone also resulted in a significantly higher estimated glomerular filtration rate, lower uric acid levels, and higher high-density lipoprotein (HDL) cholesterol, while the combined therapy additionally resulted in higher serum albumin levels, lower total cholesterol, and both atherogenic and coronary risk indexes compared with CKD control rats. The results of this study confirmed the beneficial effects of curcumin alone and provided new evidence for the beneficial effects of its combination with a reduced dose of rosuvastatin in rats with CKD and associated dyslipidemia.

Morphometric analysis of clinically significant parameters of the main trunk of the left coronary artery.

Aim To determine the value of angles between the left coronary artery main trunk (LMT) and its branches, the anterior interventricular branch (LAD) and the circumflex branch (CX), and their possible relationship with the LMT length. Methods A total of 29 cadaveric hearts were used. The left coronary artery and its branches were dissected. The hearts were then classified according to the number of branches. The LMT length was measured with a digital gauge, and the LAD-CX angle, LMTLAD angle and LMT-CX angle with a manual goniometer. Results The average value of the LMT length was 9.0 mm (6.0-13.5). In 20 (68.97%) samples, the LMT was divided into two terminal branches. There was no statistically significant difference (p=0.321) in LMT length between the hearts with a bifurcation and without it. The average value of the LAD-CX angle was 89.0° (74.5-93.0), with a statistically significant difference (p=0.020) comparing to hearts with trifurcation. The mean value of the LMT-LAD angle was 30.83±9.23° and it was significantly lower (p=0.006) in the group of hearts with bifurcation compared to the group with trifurcation of the main trunk. Conclusion The LMT length shows great variability and is not related to the LAD-CX, LMT-LAD or the LMT-CX angle. Knowledge of the left coronary variation is essential in order to avoid misinterpretation of arteriogram.

Time-dependent proregenerative effects of exogenous melatonin on the transected sciatic nerve / Efectos proregenerativos dependientes del tiempo de la melatonina exógena en el nervio ciático seccionado

SUMMARY: Microsurgical procedures are the treatment of choice of peripheral nerve injuries, but often fail to reach full functional recovery. Melatonin has neuroprotective actions and might be used as a possible proregenerative pharmacological support. Therefore, the aim of this study was to analyze the time-dependence of the neuroprotective effect of melatonin on the overall fascicular structures of both ends of the transected nerve. Sciatic nerve transection was performed in 34 adult male Wistar rats divided in four groups: two vehicle groups (N=7) treated intraperitoneally for 7 (V7) or 21 (V21) consecutive days with vehicle (5 % ethanol in Ringer solution) and two melatonin groups (N=10) administered intraperitoneally 30 mg/kg of melatonin for 7 (M7) or 21 (M21) consecutive days. At the end of the experiment, proximal stump neuroma and distal stump fibroma were excised and processed for qualitative and quantitative histological analysis. Intrafascicular neural structures were better preserved and the collagen deposition was reduced in the melatonin treated groups than in the vehicle groups. Myelin sheath regeneration observed through its thickness measurement was statistically significantly (p<0,05) more pronounced in the M21 (1,23±0,18 µm) vs. V21 group (0,98±0,13 µm). The mean volume density of the endoneurium was lower in both melatonin treated groups in comparison to the matching vehicle treated groups. Although not statistically different, the endoneural tube diameter was larger in both melatonin groups vs. vehicle groups, and the effect of melatonin was more pronounced after 21 days (24,97 % increase) vs. 7 days of melatonin treatment (18,8 % increase). Melatonin exerts a time-dependent proregenerative effect on nerve fibers in the proximal stump and an anti-scarring effect in both stumps.

Los procedimientos microquirúrgicos son el tratamiento de elección de las lesiones de los nervios periféricos, pero a menudo no logran una recuperación funcional completa. La melatonina tiene acciones neuroprotectoras y podría ser utilizada como un posible apoyo farmacológico proregenerativo. Por lo tanto, el objetivo de este estudio fue analizar la dependencia del tiempo del efecto neuroprotector de la melatonina sobre las estructuras fasciculares generales de ambos extremos del nervio seccionado. La sección del nervio ciático se realizó en 34 ratas Wistar macho adultas divididas en cuatro grupos: dos grupos de vehículo (N=7) tratados por vía intraperitoneal durante 7 (V7) o 21 (V21) días consecutivos con vehículo (5 % de etanol en solución Ringer) y dos grupos grupos de melatonina (N=10) a los que se les administró por vía intraperitoneal 30 mg/kg de melatonina durante 7 (M7) o 21 (M21) días consecutivos. Al final del experimento, se extirparon y procesaron el neuroma del muñón proximal y el fibroma del muñón distal del nervio para un análisis histológico cualitativo y cuantitativo. Las estructuras neurales intrafasciculares se conservaron mejor y el depósito de colágeno se redujo en los grupos tratados con melatonina respecto a los grupos con vehículo. La regeneración de la vaina de mielina observada a través de la medición de su espesor fue estadísticamente significativa (p<0,05) más pronunciada en el grupo M21 (1,23±0,18 µm) vs V21 (0,98±0,13 µm). La densidad de volumen media del endoneuro fue menor en ambos grupos tratados con melatonina en comparación con los grupos tratados con vehículo equivalente. Aunque no fue estadísticamente diferente, el diámetro del tubo endoneural fue mayor en ambos grupos de melatonina frente a los grupos de vehículo, y el efecto de la melatonina fue más pronunciado después de 21 días (aumento del 24,97 %) frente a los 7 días de tratamiento con melatonina (18,8 % de aumento). La melatonina ejerce un efecto proregenerativo dependiente del tiempo sobre las fibras nerviosas del muñón proximal y un efecto anticicatricial en ambos muñones.

Qualitative and quantitative characteristics of the passive compartment underneath the myocardial bridge comprising the blood vessel adventitia and the perivascular connective tissue / Características cualitativas y cuantitativas del compartimento pasivo debajo del puente miocárdico que comprende la adventicia del vaso sanguíneo y el tejido conectivo perivascular

SUMMARY: Myocardial bridges are inborn anomalies frequently found in authopsies. Although tipically clinically silent, they are occasionally associated with severe clinical manifestations, e.g. myocardial ischemia or even sudden death. The pathophysiology and risk factors for these manifestations have not yet been completely elucidated. The connective tissue underneath the bridge has been considered as one of the factors the symptoms depend on. Thus, the aim of this research was to determine the histological characteristics of the connective tissue lying underneath the myocardial bridge and to contribute to a better understanding of the protective effects this passive compartment might have in prevention of severe clinical manifestations of myocardial bridging. The study was carried out on twenty hearts with myocardial bridges. Length of the bridge was determined using a precise electronic caliper. Sections of the myocardial bridges with the underlying connective tissue were obtained and prepared for qualitative and quantitative analysis. The connective tissue underneath the bridges was composed of adipose tissue and loose connective tissue in different ratios. The tissue underneath thin bridges was predominantly composed of adipose tissue, while loose connective tissue was the dominant component under thick bridges. The myocardial bridges had an average thickness of 0,98 ± 0.44 mm and an average length of 15,25±5,65 mm. We found a strong positive correlation between the myocardial bridge thickness and length (r = 0,860, p = 0,0001). The thickness of the passive connective tissue compartment under the myocardial bridges was 0,58±0,22 mm, and there was no correlation between this parameter and the myocardial bridge thickness (r = -0,011; p = 0,963). In the clinical evaluation of patients with these anomalies it is necessary to take into account independently the myocardial bridge thickness and length on one side and the thickness of the connective tissue lying underneath it on the other.

Los puentes miocárdicos son anomalías congénitas que se encuentran con frecuencia en las autopsias. Aunque típicamente éstos son clínicamente silenciosos, ocasionalmente se asocian con manifestaciones clínicas graves, como isquemia miocárdica o incluso muerte súbita. La fisiopatología y los factores de riesgo de estas manifestaciones aún no se han dilucidado por completo. El tejido conectivo debajo del puente se ha considerado como uno de los factores de los que dependen los síntomas. Por lo tanto, el objetivo de esta investigación fue determinar las características histológicas del tejido conectivo que se encuentra debajo del puente miocárdico y contribuir a una mejor comprensión de los efectos protectores que este compartimento pasivo podría tener en la prevención de manifestaciones clínicas graves de puente miocárdico. El estudio se llevó a cabo en veinte corazones con puentes miocárdicos. La longitud del puente se determinó utilizando un calibrador electrónico preciso. Se obtuvieron secciones de los puentes miocárdicos con el tejido conjuntivo subyacente y se prepararon para análisis cualitativo y cuantitativo. El tejido conectivo debajo de los puentes estaba compuesto de tejido adiposo y tejido conectivo laxo en diferentes proporciones. El tejido debajo de los puentes delgados estaba predominantemente compuesto de tejido adiposo, mientras que el tejido conectivo laxo era el componente dominante debajo de los puentes gruesos. Los puentes de miocardio tenían un espesor promedio de 0,98 ± 0,44 mm y una longitud promedio de 15,25 ± 5,65 mm. Encontramos una fuerte correlación positiva entre el grosor y la longitud del puente miocárdico (r = 0,860, p = 0,0001). El grosor del compartimiento de tejido conectivo pasivo debajo de los puentes miocárdicos era de 0,58±0,22 mm, y no hubo correlación entre este parámetro y el grosor del puente miocárdico (r = -0,011; p = 0,963). En la evaluación clínica de pacientes con estas anomalías es necesario tener en consideración de forma independiente el grosor y la longitud del puente de miocardio por un lado y el grosor del tejido conectivo que se encuentra debajo del mismo por el otro.

Melatonin Protects the Histologic Structure of the Uterus in Conditions of Zearalenone Intake.

Background: Zearalenone is a widely spread mycotoxin, contaminant of most cereal grains. It has uterotropic, estrogenic and anabolic activity in farm animals. The results are hormonal disbalances as hyperestrogenism, Zearalenone inhibits follicle-stimulating hormone production, thus supressing ovarian follicle development and ovulation. Also, it induces oxidative stress. Melatonin acts as a potent natural antioxidant and regulates the reproductive function by modification of steroidogenesis. Objective: The present study was conducted to provide detailed qualitative histological analysis of uterus of female rats treated with zearalenone and melatonin and contribute to better understanding of the topic. Methods: Forty adult, female Wistar rats were equally divided into five groups: Z group - zearalenone, 0,3 mg/kg, i.g.; M group - melatonin, 10 mg/kg, i.p.; ZM group -concomitant application of zearalenone and melatonin in the same dosing regimen, VZ group-zearalenone vehiculum/sunflower oil, i.g. and MZ group-melatonin vehiculum/5% ethanol in Ringer, i.p. Animals were treated daily for 28 consecutive days. After that period, all animals were sacrificed to obtain samples for qualitative histological analysis using the light microscope. Results: Zearalenone led to the alterations of the uterine structures, predominantly in the endometrium that were characterized by metaplasia and hypertrophy of the epithelial cells and hypercellularity of the stroma. In the myometrium, zearalenone induced hypertrophy and hyperplasia of the myocytes. Conclusion: Melatonin, when applied together with zearalenone, blocked the adverse effects of the zearalenone.

Gender-related Histological Changes in the Thymus Gland After Pinealectomy and Short-term Melatonin Treatment in Rats.

OBJECTIVES: The aim of this study was to investigate the effects of pinealectomy and melatonin treatment on the rat thymus gland characteristics, taking into consideration possible gender differences. MATERIALS AND METHODS: Thirty adult Wistar rats of both sexes were divided into three groups. Group C and group PX served as control groups and included sham-pinealectomized and pinealectomized animals that were treated with 10% ethanol solution (0,1ml/daily, subcutaneous). Animals from third group (group PXM) underwent pinealectomy and seven days after surgery started receiving melatonin dissolved in 10% ethanol solution (3mg/kg/daily, subcutaneous). All animals were treated for 4 weeks. RESULTS: Volume density of the thymus cortex showed statistically significant (p<0,05) decrease while the volume density of the thymus medulla was increased in the pinealectomized compared to the sham-pinealectomized female rats. Numerical density of macrophages as well as the distribution of blood vessels showed no gender differences. The numerical density of lymphocytes was statistically significantly decreased in female in comparison to the male pinealectomized rats. Melatonin treatment was proved to cause reverse effects in the sense that the results from the melatonin treated group corresponded to the results obtained from the control group of animals. CONCLUSION: The results of this study suggest that the pinealectomy causes gender-related changes in the rat thymus. Short-term melatonin treatment showed reverse effect, equally in both sexes.

A histological study of the effect of exogenous melatonin on gentamicin induced structural alterations of proximal tubules in rats.

The aim of this research was to assess the reactive changes of rat proximal tubules caused by gentamicin and the effect of relatively low doses of melatonin. 48 adult male Wistar rats were distributed into six groups of equal size which all received one of the following daily intraperitoneal injections: vehicle (5% ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8 days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8 days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days (GM1, GM2) and two groups treated only with melatonin in two different doses (5 or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative and semi-quantitative light microscopy analysis of proximal tubules. Exogenous melatonin had no significant effect on the microstructure, independently of dosis. The changes of proximal tubules microstructure induced by gentamicin were expressed in the form of granulovacuolar degeneration, necrosis and desquamation. The grade of proximal tubular changes was smaller in animals who besides gentamicin received melatonin. Melatonin has a dose dependent protective effect on the structural alterations of proximal tubules of the kidney induced by gentamicin.

Connexin-dependent signaling in neuro-hormonal systems.

The advent of multicellular organisms was accompanied by the development of short- and long-range chemical signalling systems, including those provided by the nervous and endocrine systems. In turn, the cells of these two systems have developed mechanisms for interacting with both adjacent and distant cells. With evolution, such mechanisms have diversified to become integrated in a complex regulatory network, whereby individual endocrine and neuro-endocrine cells sense the state of activity of their neighbors and, accordingly, regulate their own level of functioning. A consistent feature of this network is the expression of connexin-made channels between the (neuro)hormone-producing cells of all endocrine glands and secretory regions of the central nervous system so far investigated in vertebrates. This review summarizes the distribution of connexins in the mammalian (neuro)endocrine systems, and what we know about the participation of these proteins on hormone secretion, the life of the producing cells, and the action of (neuro)hormones on specific targets. The data gathered since the last reviews on the topic are summarized, with particular emphasis on the roles of Cx36 in the function of the insulin-producing beta cells of the endocrine pancreas, and of Cx40 in that of the renin-producing juxta-glomerular epithelioid cells of the kidney cortex. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Heart-type fatty acid-binding protein and its relation with morphological changes in rat myocardial damage model induced by isoproterenol.

We have investigated heart type fatty acid binding protein (H-FABP) rat serum values at different time point following subcutaneous (s.c) isoproterenol (ISO) administration and their correlation with severity of myocardial lesion. Thirty adult, male, Wistar rats were used for this study. Six rats per group were treated with a single dose of either ISO (ISO groups, dose 100 mg/kg, s.c.) at different time point (30', 60', 120', 240') or with saline (control group). Serum H-FABP was determined by enzyme-linked immunosorbent assay (ELISA) and histological analysis was performed by hematoxylin-eosin (HE) method of staining. The first serum H-FABP increase was obtained 30' following ISO administration, but maximal value was reached after 240'. Myocardial histological changes were time-dependent and correlated with serum H-FABP values (p<0.001). The results of the study suggest that H-FABP is sensitive marker for acute rat myocardial injury and its possible inclusion in myocardial injury screening studies in rats.

Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis.

The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

[Quantification of some qualitative changes of the rabbit sciatic nerve after the application of lidocaine into the mesoneurium]. / Kvantifikacija nekih od kvalitativnih promjena ishijadicnog nerva kunica nakon aplikacije lidokaina u mezoneurijum.

Seven days after the application of 2% lidocaine (4 ml doze, the speed of application 3 ml/min, mean application pressure 15 +/- 2.47 kPa) into mesoneurium of adult rabbit sciatic nerve, a nerve segment was intravitally excided from the injection site with a length of 1 cm and qualitatively and quantitatively analyzed. Histological changes at the level of total nerve structures were found, especially of its sheaths. Epi- and interfascicular epineurium were thickened with a hipercellularity of a mononuclear inflammatory process type. On the side of application, occasional delamination of perineurium was registered. Myelinated fibers were sporadically demyelinated, followed by axon degeneration which, in thick fibers, reached a full disintegration. In general, the damages were more severe at the side of application although some zonal differences in the degree of damage (above, below and at the site of application) within individual fasciculi were expressed. A significantly higher volume density of epifascicular and interfascicular connective tissue in comparison to the control, untreted nerves, observed by the stereological analysis, may be considered as an inflammatory-repairing reaction which we identified microscopically. At the same time, we found a significantly higher volume density of endoneurium in lidocaine treated nerves.

The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland.

Pineal gland has and antistressogenic role. Its main hormone, melatonin, has radio protective effect on endocrine and other dynamic tissues. In our previous study, we have shown that pinealectomy changes the behavior of suprarenal gland in totally irradiated rats. The aim of this study is to evaluate the effect of exogenous melatonin on suprarenal gland of rats with or without pineal gland. Four months after pinealectomy (experimental group) or shampinealectomy (control group), adult Wistar male rats were daily treated with 0,2 mg of melatonin intraperitoneally, during two weeks. Thereafter, all animals were totally irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative characteristics of the suprarenal gland were studied using histological methods. The results show that exogenous melatonin had protective role on suprarenal gland in totally irradiated rats and that those effects were more pronounced in the presence of pineal gland.

[Haloperidol and its side effects on the reproductive system]. / Haloperidol i njegovi nezeljeni efekti na reproduktivni sistem.

Haloperidol (4'-fluoro-4-[4-Hydroxy-4-p-chlorophenylpiperidino]-Butyrophenone), a neuroleptic, drug is the first choice in the treatment of schizophrenia. Experimental studies on rats show that haloperidol, at female, causes: decreasing of the ovarian weight, inhibition of the ovulation, producing a state of distrust and stimulation of lobuloalveolar development of the mammary glands and increasing of serum prolactin levels in both male and female rats. At male rats haloperidol causes damage of Leydig cells and cells depletion of seminal lineage with sequels on the excretory ducts level and accessory genital glands. Our pilot researches confirm these observations. The aim of this paper is to suggest an attention of the side effects of haloperidol, that's its stricter controlled use.

Detection of neurovascular structures using injection pressure in blockade of brachial plexus in rat.

In the last few decades there has been a great development of regional anesthesia; all the postulates are defined and all the techniques of usage are perfected. However, like any other medical procedure, the block of brachial plexus carries a risk of certain unwanted complications, like possible intraneural and intravascular injections. The reason for great discrepancy between the injury of brachial plexus and other periphery nerves while performing the nerve blockade is the frequent usage of this block, but also the specific proximity of neurovascular structures in axilla. The purpose of this work is to determine the values of pressures which appear in para-neural, intraneural and intravascular injection applications of local anesthetic, and to compare those values in order to avoid cases of intraneural and intravascular injections in clinical practice with consequential complications. In experimental study there have been used 12 Wistar rats of both genders. After anesthesia with ether and mid-humoral access to the neurovascular structures in axilla, the injection of 2% lidocaine with epinephrine was performed with the help of automatic syringe charge. The needle was at first placed para-neural, and then also intraneural and intravascular. During every application the pressure values were monitored using the manometer, and then they were analyzed by special software program. All para-neural injections resulted with the pressure between 13,96-27,92 kPa. The majority of intraneural injections were combined with the injection pressure greater than 69,8 kPa, while the intravascular injections were combined with injection pressure less than 6,98 kPa. Based on the available data it can be noticed that so far none of the methods of prevention from unwanted complications of regional anesthesia can insure the avoidance of intraneural and intravascular injection of local anesthetic. Based on our research it is obvious that the measuring of pressure during the nerve blockade is very important in order to decrease the risk of neurological and possible systematic complications. It is also clear that a small, mobile, and financially quite available apparatus for pressure measurement can help in differentiation between para-neural, intraneural and intravascular injection. Avoiding high injection pressure prevents from lodging the needle into intraneural space, while avoiding a very low injection pressure prevents from lodging the needle into intravascular space followed by consequential complications. The usage of this apparatus can find its application in other blockades of periphery nerves, and in other branches of medicine as well.

Histological changes of the sciatic nerve in dogs after intraneural application of lidocaine--relation to the established application pressure.

Histological changes of sciatic nerve in adult dogs 7 days after single application of 2% lidocaine (4 ml dose, speed of injection 3 ml/min) and measurement of the application pressure was studied, with a goal to investigate structural changes of the nerve in relation to the established pressure values. The application pressure was determined by using Bio Bench software. In intrafascicular puncture an average application pressure of 198.23 +/- 52 kPa was found, and in interfascicular puncture its average value was 53.3 +/- 17.9 kPa, with a note that individual differences are regularly present. Seven days after the injection, a nerve dissection was performed and serial sections covering the region of injection's puncture and bordering proximal and distal zones, in the total length of 3 cm, were prepared. The found changed show the presence of nerves' fibers lesions with a strong reactivity of Schwann's cell, as well as the change of interstitial structure concerning hypercellularity and occurrence of cellular extravasation. The covering system of the nerve in the zone of epineurium manifests changes of inflammatory process and in perineurium a decomposition of lamella layers and the alteration of their tinctorial properties were noticed. A comparison of the found nerve reactivities in intra- and interfascicular application showed their one-way alteration, although the lesions were more noticeable in the conditions of intrafascicular application. The damages were mostly expressed in the zone of local application of anesthetic, than distally from it, while the damage to the structure in the proximal part is of the smallest degree.

Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs.

BACKGROUND: Unintentional intraneural injection of local anesthetics may cause mechanical injury and pressure ischemia of the nerve fascicles. One study in small animals showed that intraneural injection may be associated with higher injection pressures. However, the pressure heralding an intraneural injection and the clinical consequences of such injections remain controversial. Our hypothesis is that an intraneural injection is associated with higher pressures and an increase in the risk of neurologic injury as compared with perineural injection. METHODS: Seven dogs of mixed breed (15-18 kg) were studied. After general endotracheal anesthesia, the sciatic nerves were exposed bilaterally. Under direct microscopic guidance, a 25-gauge needle was placed either perineurally (into the epineurium) or intraneurally (within the perineurium), and 4 mL of lidocaine 2% (1:250,000 epinephrine) was injected by using an automated infusion pump (4 mL/min). Injection pressure data were acquired by using an in-line manometer coupled to a computer via an analog digital conversion board. After injection, the animals were awakened and subjected to serial neurologic examinations. On the 7th day, the dogs were killed, the sciatic nerves were excised, and histologic examination was performed by pathologists blinded to the purpose of the study. RESULTS: Whereas all perineural injections resulted in pressures < or =4 psi, the majority of intraneural injections were associated with high pressures (25-45 psi) at the beginning of the injection. Normal motor function returned 3 hours after all injections associated with low injection pressures (< or =11 psi), whereas persistent motor deficits were observed in all 4 animals having high injection pressures (> or =25 psi). Histologic examination showed destruction of neural architecture and degeneration of axons in all 4 sciatic nerves receiving high-pressure injections. CONCLUSIONS: High injection pressures at the onset of injection may indicate an intraneural needle placement and lead to severe fascicular injury and persistent neurologic deficits. If these results are applicable to clinical practice, avoiding excessive injection pressure during nerve block administration may help to reduce the risk of neurologic injury.

[Retinal and pineal melatonin--from a circadian signal to therapeutic use]. / Retinalni i pinealni melatonin--od cirkadijalnog signala do terapijske upotrebe.

Melatonin, the major product of the pincal gland, is also synthesized in the retina of several vertebrate species. Retinal melatonin levels show a marked daily variation, with high levels at night and low levels during the light period. Melatonin rhythm generating system includes photodetector, circadian clock and melatonin synthesis machinery and they are located in pincal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). In mammals, circadian system is comprised of three major components: the eyes, the hypothalamic suprachiasmatic nucleus (SCN) and the pincal gland. The SCN harbours the endogenous oscillator that is entrained every day to the ambient lighting conditions via retinal input. Among the many circadian rhythms in the body that are driven by SCN output, the synthesis of melatonin in the pincal gland functions as a hormonal message encoding for the duration of darkness. Dissemination of this circadian information relies on the activation of melatonin receptors, which are most prominently expressed in the SCN, and the hypophysical pars tuberalis (PT), but also in many other tissues. Melatonin is essential for rhythmic signaling in the PT. Here, melatonin acts in concert with adenosine to elicit rhythms in clock gene expression. By sensitizing adenylyl cyclase, melatonin opens a temporally-restricted gate and thus lowers the threshold for adenosine to induce cAMP-sensitive genes. This interaction, which regulates gene expression and pituitary output (by endocrine-endocrine interaction) represents general mechanism by which the master clock in the brain synchronizes clock cells in peripheral tissues that require unique phasing of output signals.