Biomedical subjects

R Sheen

Publications and source records attributed to R Sheen.

18 recordsLinked to original sources

PubMed2006

Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: tiapride vs. pyridostigmine.

Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 microMol paraoxon (approximately LD75) groups 2-6 received in addition: G(2)50 microMol tiapride 30 min before paraoxonG(3)50 microMol tiapride 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G41 microMol pyridostigmine 30 min before paraoxon G(5)1 microMol pyridostigmine 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G(6)50 microMol pralidoxime 1 min after paraoxon. Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G3) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G5). Tiapride pretreatment only (G2) is inferior to pyridostigmine pretreatment only (G4). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G4 and G6).

Acute Disease↗

PubMed2006

The effects of age and streptozotocin diabetes on the sympathetic innervation in the rat penis.

The objective was to describe the changes in catecholamine levels, noradrenaline (NA) release and the ultrastructural and immunohistochemical changes in the sympathetic nerves in the penis of STZ-diabetic rats. Amines were measured using HPLC. Nerves were studied using immunocytochemistry for tyrosine hydroxylase, and electron microscopy. Diabetic animals were compared with age-matched controls. The concentration of penile NA increases at least 2.5-fold after about 10 weeks of hyperglycaemia, is maintained for over 40 weeks. The rate of release of NA in the diabetics also increases approximately by fourfold. Immunohistochemical staining for tyrosine hydroxylase showed either no change or an increase in the levels of the enzyme around the central arteries and the outer coverings of the corpus cavernosum. Cavernosal nerves show increased intensity of staining for tyrosine hydroxylase, and the presence of dilated nerve fibres and engorged endings. The axons of the dorsal nerve of the diabetic penis have a smaller cross-sectional area that is most marked in unmyelinated axons. In the diabetic penis, the nerve endings appear to contain significantly more NA than the controls, and the turnover of noradrenaline is increased substantially. There is immunocytochemical evidence of an increase in staining for tyrosine hydroxylase, suggesting an increase in synthetic activity. These results are discussed in relation to the existing literature on the role of amines in normal and disordered erectile function. In particular, the increased concentration and turnover of NA in the diabetic rat contrasts with the fall in NA in cavernosal blood described during normal erection in humans.

Aging↗

PubMed2006

HPLC analysis of K-48 concentration in plasma.

K-48 is a new oxime-type compound to be used as an enzyme reactivator in the treatment of exposure to organophosphorous compounds. Plasma concentration of K-48 can be determined using reversed-phase HPLC. Analysis using octyl silica stationary phase and ultraviolet-absorbance detection is fast and simple. K-48 displays a relatively high dose-normalized area under the curve as compared to pralidoxime, which might be beneficial for an antidote. After i.m. administration of 50 mumol K-48, the time course of the concentration can be approximated by a straight line between 15 and 120 min meaning the elimination follows zero-order kinetics.

Animals↗

PubMed2006

High-performance liquid chromatographic determination of the plasma concentration of K-27, a novel oxime-type cholinesterase reactivator.

A simple and reliable HPLC method for the determination of the plasma level of K-27, an oxime type antidote of use in organophosphorus poisoning is presented. Separation was carried out by HPLC using an octyl silica stationary phase and a mobile phase consisting of 93% phosphate buffer (pH 2.6) containing octane sulfate sodium salt, and 7% methanol. Quantitative absorbance was monitored at 286 nm. The calibration curve was linear through the range of 1.25-200 microg/mL, that is well beyond the detected plasma level range of K-27. Limit of quantitation was 5 microg/mL. Intra-day and inter-day precisions of the HPLC determinations gave standard deviations as 0.77 and 2.67%, respectively. Following intramuscular administration of 50 micromol (22.31 mg) K-27 in rats, the maximum of K-27 concentration in plasma was reached at about 15 min giving 186 microg/mL and the t(1/2) was 85 min. K-27 displays initial (from 15 trough 120 min) zero order elimination kinetics. Similar results have been found after intraperitoneal administration.

Animals↗

PubMed2006

Tiapride pre-treatment in acute exposure to paraoxon: comparison of effects of administration at different points-in-time in rats.

INTRODUCTION: Accidental and suicidal exposures to organophosphorus compounds (OPC) are frequent. The inhibition of esterases by OPC leads to an endogenous ACh poisoning. Recently, the FDA approved, based on animal experiments, for military combat medical use oral pyridostigmine (PSTG) for pre-exposure treatment of soman; the concept is to block the cholinesterase reversibly using the carbamate pyridostigmine in order to deny access to the active site of the enzyme to the irreversible inhibitor (OPC) on subsequent exposure. We have shown previously that tiapride (TIA) is in vitro a weak inhibitor of AChE. We also have shown recently that in rats coadministration of TIA with the organophosphate paraoxon significantly decreases mortality without having an impact on red blood cell cholinesterase (RBC-AChE) activity. PURPOSE OF THE STUDY: To establish in a prospective, non-blinded study in a rat model of acute high dose OPC (paraoxon; POX) exposure the ideal point in time for TIA pre-treatment administration and to correlate it with measured TIA plasma levels. MATERIAL AND METHODS: There were six groups of rats in each cycle of the experiment and each group contained six rats. The procedure was repeated twelve times (cycles) (n = 72 for each arm; half male and half female). All substances were applied ip. All groups (1-6) received 1 microMol POX ( approximately LD(75)); groups 1-5 also received 50 microMol TIA at different points in time. Group 1 (G(1)): TIA 120 min before POX Group 2 (G(2)): TIA 90 min before POX, Group 3 (G(3)): TIA 60 min before POX, Group 4 (G(4)): TIA 30 min before POX, Group 5 (G(5)): TIA & POX simultaneously, Group 6 (G(6)): POX only. The animals were monitored for 48 hours and mortality/survival times were recorded at 30 min, 1, 2, 3, 4, 24 and 48 h. AChE activities were determined at 30 min, 24 and 48 h in surviving animals. Statistical analysis was performed on the mortality data, cumulative survival times and enzyme activity data. Mortality data was compared using Kaplan-Meier plots. Cumulative survival times and enzyme activites were compared using the Mann-Whitney rank order test. No Bonferroni correction for multiple comparisons was applied and an alpha < or= 0.05 was considered significant. RESULTS: Mortality is statistically significantly reduced by TIA pre-treatment at all points-in-time. Highest protection is achieved if TIA is given 90 to 0 min before OPC exposure. The reduction in mortality is not correlated to TIA plasma levels (C (max) approximately 120 min post ip-administration). TIA pre-treatment is not affecting AChE activity regardless of the timing of administration. CONCLUSION: The lack of correlation between TIA plasma levels and degree of mortality reduction as well as the lack of protective effect on enzyme activity seem to indicate that the site of action of TIA is not the blood. While our hypothesis that TIA would protect AChE in a pyridostigmine-like manner (via protection of the enzyme) could not be confirmed, the reduction in mortality with TIA pre-treatment is nevertheless of potential interest.

Animals↗

PubMed2004

Effects of age and streptozotocin-induced diabetes on biogenic amines in rat tail artery.

The changes in amine concentrations in different segments of the rat tail artery have been investigated at different ages and after different durations of streptozotocin-induced diabetes. There was a significant positive slope to the relationship between amine concentrations and age in proximal portion of the normal tail artery, and a significant additional increase in amine concentrations following induction of diabetes. The peak of the latter response occurred between 10 and 20 weeks following the induction of diabetes. There was also a significant dependence on the length of the post-ganglionic neurones, which may be related to the failure of axonal transport of some of the essential enzymes or transporters for these biogenic amines. This model of altered catecholamine metabolism and handling requires further investigation so that alterations in the mechanisms involved in processing of these amines in diabetic autonomic neuropathy may be elucidated.

Age Factors↗

PubMed2001

Catecholamines in the heart and adrenal gland of the STZ-diabetic rat.

The concentrations of noradrenaline (NA), adrenaline (ADR), 5-hydroxyindoleacetic acid (5-HIAA), serotonin (5-HT) and dopamine (DOP) have been studied in the left ventricle and the left adrenal gland of control and streptozotocin (STZ) - treated rats at various intervals (12, 24, 30, 34, 38 and 42 weeks) after the induction of diabetes. The only amines detected in the heart were NA, 5-HIAA and DOP, whereas those detected in the adrenal gland were NA and ADR. Differential changes in the catecholamine concentrations occurred in the heart and the adrenal gland at different stages of the metabolic disorder. In the heart the initial changes in short-term diabetes included an increase in NA concentration but this did not persist in the longer term diabetic animals (30-38 weeks following STZ injection). In the adrenal gland there was an initial reduction followed by a steady increase in the concentration of NA and ADR throughout the period of the study.

Adrenal Glands↗

PubMed2001

Streptozotocin-Induced diabetes mellitus is associated with increased pancreatic tissue levels of noradrenaline and adrenaline in the rat.

The pancreata of streptozotocin-induced diabetic rats were examined to determine whether the pancreatic tissue content of catecholamines is altered after the onset of diabetes. Experimental diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). Four weeks after the induction of diabetes, pancreatic tissue fragments were taken from the tail end of the pancreas and processed for catecholamine content using the high-performance liquid chromatography method. Immunohistochemical analysis showed that the pancreata of diabetic rats contained more tyrosine hydroxylase-positive nerves compared with controls. Pancreatic noradrenaline content, expressed as the mean +/- SD, was significantly (p < 0.03) greater in diabetic rats (54+/-11.74 pg x mL(-1) x mg tissue(-1)) compared with normal, sex- and age-matched control rats (37.54+/-1.18 pg x mL(-1) x mg tissue(-1)). Similarly, the adrenaline content in diabetic rat pancreatic tissue (102.69+/-20.24 pg x mL(-1) mg tissue(-1)) was markedly greater (p < 0.003) compared with sex- and age-matched controls (35+/-9.23 pg x mL(-1) x mg tissue(-1)). In contrast, 5-hydroxyindole acetic acid decreased significantly (p < 0.0002) in diabetic pancreatic tissue (13.41+/-0.87 pg x mL(-1) x mg tissue(-1)) compared with controls (80.72+/-1.46 pg x mL(-1) x mg tissue(-1)). The plasma levels of these catecholamines also increased slightly but not significantly in diabetic rats compared with controls. These results suggest that diabetes is associated with increased noradrenaline and adrenaline and decreased 5-hydroxyindole acetic acid pancreatic tissue levels. These disturbances in catecholamine metabolism may play a role in the pathogenesis of the acute and chronic complications of diabetes mellitus.

Animals↗

PubMed1994

Reconstruction of intraoral mucosal defects with revascularized jejunal segments.

The intraoral mucosa subserves a multitude of structural and functional roles. This paper details the importance of this within the context of reconstruction. The various methods are reviewed historically. Also, both the experimental and clinical basis for using revascularized jejunum as mucosal reconstruction are presented.

Animals↗

PubMed1994

In the absence of periosteum, transplanted fetal and neonatal rat coronal sutures resist osseous obliteration.

Normal craniofacial development depends on expansion of the cranial vault by growth at the sutures. Inappropriate development of the sutures leads to global disruption of patterns of craniofacial growth. Tissue interactions between dura mater and suture matrix play a critical role in the phenotypic maintenance of cranial sutures. However, the function of the periosteum in this process remains under-reported and controversial. To examine the contribution of periosteum in maintaining the patency of coronal sutures, fetal and neonatal rat coronal sutures were transplanted to surgically created defects in adult rat host parietal bones. These sutures were examined for their ability to persist in the host milieu in the presence and absence of both donor and host periosteum. This study established that removal of both host and transplant periosteum, unlike removal of dura mater, did not lead to obliteration of either fetal or neonatal sutures. Thus, periosteum and dura mater are nonequivalent tissues with respect to influence on suture patency.

Animals↗

PubMed1990

Surgical correction of Crouzon syndrome.

This study analyzes the results of surgical treatment in 39 patients with the Crouzon syndrome. Early fronto-orbital advancement and craniectomy were universally successful in relieving raised intracranial pressure and in reducing ocular proptosis. However, definitive cosmetic correction was not achieved, and early cranial surgery was not able to prevent the development of midface hypoplasia. Thirty-two midfacial advancements have been performed in 30 patients. Sixteen patients had sufficient follow-up data for more than 2 years postoperatively. In all patients, a satisfactory early postoperative result was achieved. In the long-term follow-up group, 11 patients have maintained a satisfactory appearance, while 5 have developed recurrent deformity. Analysis shows this to be associated with a younger age at operation and continued mandibular growth. Frontofacial advancement in adults achieves good long-term results but is associated with a higher incidence of complications.

Adolescent↗

PubMed1989

Hydrocephalus in Crouzon's syndrome.

We reviewed 42 cases of Crouzon's syndrome. There were 16 cases with ventricular dilation. We believe that shunt should be inserted after fronto-orbital advancement if there are persistent signs of raised intracranial pressure. However, in cases presenting with severe ventricular dilation and papilloedema, a shunt is inserted prior to fronto-orbital advancement. Medium- or high-pressure systems should be used.

Cerebrospinal Fluid Shunts↗

PubMed1989

Lower limb reconstruction in children using expanded free flaps.

Controlled expansion is a technique that increases the area of local tissue available for reconstruction. An extension of this is to expand free flaps prior to elevation, thereby increasing their area. This has been particularly useful in children where there may be insufficient tissue available at free flap donor sites. Four children have had extensive cutaneous defects of the lower limb reconstructed with expanded parascapular free flaps. Measurements indicate an approximate doubling in skin area. There has been normal growth of the affected limbs and there has been no donor site morbidity. Apart from small areas of narrow marginal necrosis at the tip of the flaps in the first three cases, which were of no consequence, healing at the recipient site was complete.

Child↗

PubMed1988

Microvascular ear replantation.

Three cases of attempted ear replantation are presented. Successful revascularisation was achieved in all patients. However, in one case venous congestion and necrosis of the ear occurred at 7 days. Thorough initial debridement of skin and cartilage plus systemic heparinisation and haemodilution upon completion of the vascular anastomoses are considered important technical factors. When compared with other forms of reconstruction, ear replantation gives a superior result and is therefore advocated whenever possible.

Adult↗

PubMed1988

Intraoral mucosal reconstruction with microvascular free jejunal autografts: an experimental study.

This experimental study investigated the problem of covering bare bone adequately in the oral cavity to provide a stable, functionally acceptable reconstruction. In eight dogs, intraoral mucosal defects were created whilst preserving the mandibular arch. The defects were reconstructed with a microvascular jejunal patch. Six animals had their reconstructions stressed postoperatively by the administration of irradiation and by feeding solid food. Two control dogs did not receive irradiation. Grafts were assessed clinically and histologically for 6 months. Rapid mucosal healing occurred in seven of eight dogs. The grafts conformed well to the mandibular contour and were tolerant of postoperative radiotherapy and the chewing of solid food. Structural integrity of seven grafts was maintained although subtotal villous atrophy occurred in irradiated grafts and to a lesser extent in control grafts. In one animal whose graft mucosa sloughed, the wound was re-epithelialized from the adjacent buccal mucosa. Microvascular jejunal patches therefore provided a durable, functionally adequate reconstruction of the mouth floor.

Animals↗

PubMed1988

Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study.

A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident.

Animals↗

PubMed1988

Mandibular reconstruction with vascularized iliac crest: a 10-year experience.

Since 1978, 35 patients have undergone mandibular reconstruction with vascularized iliac crest. During this time, the technique of raising and shaping the iliac crest has undergone a series of modifications. Initially, osteocutaneous segments based first on the superficial circumflex iliac system and later on the deep circumflex iliac system were used. More recently, only the inner table of the ilium has been employed, and where intraoral lining is required, an ulnar forearm free flap has been added. Thirty-two patients were reconstructed successfully. Of the three anastomotic failures, one bony segment was able to survive as a free graft. There were no donor-site complications. With continued experience, operative morbidity has been minimized, while the technique has been modified to tailor the reconstruction to the specific requirements of the patient. It is concluded that vascularized iliac crest provides the most appropriate mandibular reconstruction for a range of congenital and acquired defects.

Adolescent↗

PubMed1987

Intraluminal pH measurement to monitor the vascular perfusion of free jejunal autografts: an experimental study.

An evaluation of the effect of ischaemia upon the intraluminal pH of microvascular free jejunal autografts was undertaken with a view to developing a monitoring system to be used clinically. Employing a canine model, the intraluminal pH of isolated jejunal segments was measured during normal perfusion and under conditions of arterial and venous occlusion. Ischaemia induced a rapid, easily measured fall in intraluminal pH reversible after 1 h of normothermic ischaemia. The most rapid pH change occurred within the first 10 min. It is felt that continuous intraluminal pH measurement may form a reliable method of monitoring the postoperative vascular perfusion of clinical free jejunal transfers.

Animals↗