Evaluation of effect of cyclosporine A on the bone tissue with induced periodontal disease to ligature in rats.

The administration of cyclosporine A (CsA) has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of CsA on alveolar bone of rats subjected to experimental periodontitis, using histomorphometric and histological analysis. Twenty-four rats were divided into groups with 6 animals each: 1, control; 2, rats with ligature around the lower first molars; 3, rats with ligature around the lower first molars and that were treated with 10 mg CsA/kg of body weight/d; and 4, rats treated with 10 mg CsA/kg of body weight/d. At the end of 30 days, rats were humanely killed and subjected to a histological processing, with analysis of the distance cemento-enamel junction and alveolar bone crest, bone area, eroded bone area, and cemento surface. All of them were assessed at the mesial region of the alveolar bone. The CsA therapy combined with ligature placement decreased bone area and increased the eroded bone area around the tooth surface. The results at the histological analysis showed the same combination and changes. Therefore, in spite of the lack of a direct effect on the alveolar bone height, the CsA therapy intensified the imbalance of the alveolar bone homeostasia in a rat model of experimental periodontitis.

Effects of long-term FK 506 therapy on the alveolar bone and cementum of rats.

Cyclosporine (CsA) and tacrolimus (FK 506) exert complex, incompletely understood actions on bone. The objective of the study was to evaluate the effects of long-term tacrolimus therapy on the periodontium. Rats were treated for 60, 120, 180, and 240 days with daily subcutaneous injections of 1 mg/kg body weight of FK 506. After the experimental period, we obtained serum levels of calcium and alkaline phosphatase (ALP). After histological processing, the alveolar bone and cementum, as well as volume densities of bone (V(b)) and osteoclasts (V(o)), were assessed at the regions of the lower first molar. There was a tendency toward a statistically significant decrease in ALP levels with FK 506; however, serum calcium levels increased during the long periods. At 60, 180, and 240 days of treatment with FK 506, we did not observe V(b) and V(o) alterations. At 120 days of treatment, there was an evident decrease in V(b), but it did not show alveolar bone loss. We did not observe any alterations of cementum among rats treated with FK 506. It may be concluded that FK 506 administration did not induce side effects on the periodontium.

Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats.

BACKGROUND AND OBJECTIVE: Cyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease. MATERIAL AND METHODS: Groups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca(2+)), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1beta, prostaglandin E(2) and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed. RESULTS: Treatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent. CONCLUSION: This study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1beta and prostaglandin E(2) production.

Treatment with tacrolimus enhances alveolar bone formation and decreases osteoclast number in the maxillae: a histomorphometric and ultrastructural study in rats.

Recent studies have suggested that tacrolimus monotherapy is a beneficial therapeutic alternative for the normalization of cyclosporin-induced bone loss in animal models and humans. The mechanism accounting for this action is unclear at present. In the present study, we attempted to determine the effect of tacrolimus monotherapy on alveolar bone using histological, histomorphometric and transmission electron microscopy (TEM). Groups of rats (n=10 each) were treated with either tacrolimus (1mg/kg/day, s.c.) or drug vehicle for 60 days. Fragments containing maxillary molars were processed for light microscopy to investigate the alveolar bone volume, trabecular separation, number of osteoclasts and osteoblasts, and transmission electron microscopy to investigate their ultrastructural basic phenotype. Treatment with tacrolimus monotherapy during 60 days may induce increases in alveolar bone volume (BV/TV,%; P<0.05) and a non-significant decrease in trabecular separation (Tb.Sp,mm; P>0.05), represented by a decrease in osteoclast number (N.Oc/BS; P<0.05) and maintenance of osteoblast number (N.Ob/BS; P>0.05). Osteoblasts were often observed as a continuous layer of active cells on the bone surface. Osteoclasts appeared to be detached from the resorbed bone surface, which was often filled by active osteoblasts and collagen-rich matrix. Moreover, osteoclasts in the treated group were frequently observed as inactive cells (without ruffled border, clear zone and detached from the bone surface). Within the limits of the present study, we conclude that tacrolimus leads to an increase in alveolar bone formation, which probably exerts action on osteoclasts. Tacrolimus could, therefore, play a crucial role in the control of both early osteoclast differentiations from precursors, as well as in functional activation.

The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats--a morphological evaluation.

BACKGROUND: Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies. OBJECTIVE: The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats. MATERIALS AND METHODS: Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar. RESULTS: After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P>0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the Vf and Vcf (P<0.05). CONCLUSIONS: Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related.

Alendronate therapy in cyclosporine-induced alveolar bone loss in rats.

BACKGROUND AND OBJECTIVE: Cyclosporine A is an immunosuppressive drug that is widely used in organ transplant patients as well as to treat a number of autoimmune conditions. Bone loss is reported as a significant side-effect of cyclosporine A use because this can result in serious morbidity of the patients. As we have shown that cyclosporine A-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effect of the concomitant administration of alendronate on alveolar bone loss in a rat model. MATERIAL AND METHODS: Forty Wistar rats (10 per group) were given cyclosporine A (10 mg/kg, daily), alendronate (0.3 mg/kg, weekly), or both cyclosporine A and alendronate, for 60 d. The control group received daily injections of sterile saline. The expression of proteins associated with bone turnover, including osteocalcin, alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP), and also the calcium levels, were evaluated in the serum. Analysis of the bone volume, alveolar bone surface, the number of osteoblasts per bone surface and the number of osteoclasts per bone surface around the lower first molars was also performed. RESULTS: The results indicate that cyclosporine A treatment was associated with bone resorption, represented by a decrease in the bone volume, alveolar bone surface and the number of osteoblasts per bone surface and by an increase in the number of osteoclasts per bone surface and TRAP-5b. These effects were effectively counteracted by concomitant alendronate administration. CONCLUSION: It is concluded that concomitant administration of alendronate can prevent cyclosporine A-associated alveolar bone loss.

Protective effects of Tacrolimus, a calcineurin inhibitor, in experimental periodontitis in rats.

OBJECTIVE: Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease. DESIGN: Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days. RESULTS: Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1beta, TNF-alpha and IL-6. CONCLUSIONS: The effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease.

Influence of age on combined effects of cyclosporin and nifedipine on rat alveolar bone.

BACKGROUND: There is some evidence showing that cyclosporin A (CsA) and nifedipine (NIF) affect bone metabolism. The purpose of this work was to study the effects of CsA and NIF, given alone or concurrently, on alveolar bone of rats of different ages. METHODS: Rats 15, 30, 60, and 90 days old were treated daily with 10 mg/kg body weight of CsA subcutaneously injected and/or 50 mg/kg body weight of NIF/day given orally for 60 days. Alveolar bone of the first lower molars was morphologically and stereologically evaluated in serial 5 microm bucco-lingual paraffin sections, stained with hematoxylin and eosin. Serum calcium and alkaline phosphatase levels were measured in all animals at the end of the experimental period. RESULTS: Rats treated with CsA or NIF alone or CsA and NIF concurrently showed decreased alveolar bone density. CsA was more effective than NIF. A significant decrease in serum calcium was found only in animals treated with CsA or CsA/NIF. The results were similar regardless of age. CONCLUSIONS: These results indicate that the decrease in the alveolar bone volume in rats caused by CsA and NIF alone or concurrently is not age dependent. Furthermore, NIF (50 mg/kg) did not further increase the loss of alveolar bone volume induced by CsA (10 mg/kg).

Effect of cyclosporin A on alveolar bone homeostasis in a rat periodontitis model.

OBJECTIVES: The administration of cyclosporin A has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of cyclosporin A on alveolar bone of rats subjected to experimental periodontitis, using serum, stereometric and radiographic analysis. METHODS: Twenty-four rats were divided into one of the following groups with six animals each: group I, control rats; group II, in which the animals received a cotton ligature around the lower first molars; group III, in which the rats received a cotton ligature around the lower first molars and were treated with 10 mg/(kg body weight day) of cyclosporin A; group IV, in which the rats were treated with 10 mg/(kg body weight day) of cyclosporin A. At the end of experimental period, at 30 days, animals were killed and the serum calcium and alkaline phosphatase levels were measured in all groups. The distance from the alveolar bone crest to the cemento-enamel junction was measured radiographically for each mesial surface of the lower first molars of each rat. After histological processing, the stereological parameters: volume densities of multinucleated osteoclasts (V(o)), alveolar bone (V(b)), marrow (V(m)), and relation of eroded surface/bone surface (Es/Bs) were assessed at the mesial region of the alveolar bone. RESULTS: Significant decreases in serum calcium were observed in those groups that received cyclosporin A therapy. No significant changes in serum alkaline phosphatase were observed. The therapy with cyclosporin A combined with the ligature placement decreased the V(b) and increased the V(o), V(m) and Es/Bs at the mesial surface of lower first molars. On the other hand, the radiographic data showed that cyclosporin A therapy diminished the alveolar bone loss at the mesial surface of the lower first molars. CONCLUSIONS: Therefore, within the limits of this study, we suggest that cyclosporin A at immunosuppressive levels can bring about an imbalance in the alveolar bone homeostasis in rats. However, in the presence of inflammatory stimulation, the inhibition of the immune system by cyclosporin A may decrease the initial periodontal breakdown.

Interplay between nitric oxide and vasoactive intestinal polypeptide in inducing fluid secretion in rat jejunum.

Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the regulation of neuromuscular function in the gut. They are also potent intestinal secretogogues that coexist in the enteric nervous system. The aims of this study were: (1) to investigate the interaction between NO and VIP in inducing fluid secretion in the rat jejunum, and (2) to determine whether the NO effect on intestinal fluid movement is neurally mediated. The single pass perfusion technique was used to study fluid movement in a 25 cm segment of rat jejunum in vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole (L-NI)) and the VIP antagonist ([4Cl-D-Phe6,Leu17]VIP (VIPa)) on L-arginine-induced changes in fluid movement, expressed as microl min(-1) (g dry intestinal weight)(-1), was determined. In addition, the effect of neuronal blockade by tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced a significant fluid secretion (-14 (-20 to -5); P<0.01). This effect was reversed completely by L-NAME (60 (36-65); P<0.01) and L-NI (46 (39-75); P<0.01) and partially by VIPa (37 (14-47); P<0.01). TTX and BAC partially inhibited the effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P<0.05). The effect of VIP on fluid movement (-23 (-26 to -14)) was partially reversed by L-NAME (24 (8.4-35.5); P<0.01) and L-NI (29 (4-44); P<0.01). The inhibition of VIP or NO synthase prevented L-arginine- and VIP-induced intestinal fluid secretion through a neural mechanism. The data suggest that NO enhances the release of VIP from nerve terminals and vice versa. Subsequently, each potentiates the other's effect in inducing intestinal fluid secretion.

Experimental colitis decreases rat jejunal amino acid absorption: role of capsaicin sensitive primary afferents.

Ulcerative colitis and experimental colitis are known to be associated with functional and structural abnormalities of the small intestine. The aim of this study was to determine whether experimental colitis in the rat has any effect on jejunal amino acid absorption and to investigate the neural mechanisms involved. In Sprague Dawley rats, colitis was induced by intracolonic administration of 0.1 ml of 6% iodoacetamide. Alanine absorption in the jejunum was measured using the single pass intraluminal perfusion technique in vivo and the three-compartment model in vitro. Experiments were done in normal and sham treated rats, as well as in rats that underwent neonatal capsaicin treatment, adult capsaicin treatment, or subdiaphragmatic vagotomy. Colitis was more severe in rats subjected to neonatal or adult capsaicin treatment, but was not affected by subdiaphragmatic vagotomy. In rats with colitis, jejunal alanine absorption was reduced by 2% (P>0.05), 28%, 40%, and 18% (P<0.001) at 1, 1.5, 2, and 3 days post rectal iodoacetamide administration. A rebound increase of 12% above baseline was noted at 4 days (P<0.05). Similar results were noted in vitro. In rats that received two consecutive injections of iodoacetamide, the decrease in jejunal alanine absorption occurred earlier, was more severe, and persisted for more than 30 days. Neonatal as well as adult capsaicin treatment aggravated both the colitis and the decrease in jejunal alanine absorption. On the other hand, subdiaphragmatic vagotomy attenuated the decrease in jejunal alanine absorption, but had no significant effect on colitis severity. It is concluded that iodoacetamide induced colitis impairs jejunal amino acid absorption and that this effect involves vagal efferents as well as capsaicin sensitive primary afferents.

Effect of vasoactive intestinal polypeptide (VIP) antagonism on rat jejunal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

BACKGROUND: The enteric nervous system is important in the pathophysiology of intestinal fluid secretion induced by cholera toxin (CT), Escherichia coli heat labile (LT), and heat stable (STa) toxins. The neurotransmitters involved are not fully elucidated. Vasoactive intestinal polypeptide (VIP), a potent intestinal secretagogue present in the enteric nervous system, is increased after exposure of the cat intestine to CT. Whether VIP is involved in the pathogenesis of cholera and other toxins in not known. AIM: To study in vivo the effect of VIP antagonism on jejunal fluid secretion induced by CT, LT, and STa. METHODS: CT, LT (25 microg), or 0.9% NaCl was instilled in an isolated 25 cm segment of rat jejunum, and the VIP antagonist (VIPa) [4Cl-D-Phe(6), Leu(17)]-VIP (0.2 or 2 microg/kg/min) or 0.9% NaCl was given intravenously. Two hours later, single pass in vivo jejunal perfusion was performed to assess fluid movement. In STa experiments, intravenous VIPa or 0.9% NaCl was given and 30 minutes later the jejunal segment was perfused with a solution containing STa 200 microg/l. RESULTS: VIPa had no effect on basal intestinal fluid absorption. CT induced net fluid secretion (median -68 microl/min/g dry intestinal weight (interquartile range -80 to -56)) which was dose dependently reversed by VIPa (6.2 (-16 to 34) and 29 (17 to 42); p<0.01). Similarly, LT induced secretion (-63 (-73 to -30)) was attenuated by VIPa (0.2 microg/kg/min) (-15 (-24 to -1); p<0.01) and totally reversed to normal levels by VIPa (2 microg/kg/min) (37 (28-56); p<0. 01 compared with LT and not significant compared with normal controls). STa induced secretion (-17 (-19 to -2)) was also reversed by VIPa (12 (9-23) and 14 (0-26); p<0.01). CONCLUSION: VIP plays an important role in CT, LT, and STa induced intestinal secretion and may be the final putative neurotransmitter in the pathophysiology of these toxins.

Calcitonin gene-related peptide regulates amino acid absorption across rat jejunum.

The calcitonin gene related peptide (CGRP) is widely distributed in the enteric nervous system and gut afferents. Its role in normal digestion and absorption is not characterised. This study is conducted to elucidate whether CGRP regulates amino acid absorption in the small intestine. In in vivo experiments using the single-pass perfusion technique, intravenous infusion of CGRP (250-750 pmol/kg-min) reduced alanine absorption by 35-40%. The effects were completely blocked by the antagonist hCGRP (8-37). Moreover, intravenous infusion of CGRP antagonist blocked the inhibitory effect of intraluminal capsaicin perfusion on alanine absorption. Similarly, intracerebral injection of CGRP decreased alanine absorption, an effect which was reduced by vagotomy. In vitro experiments using isolated jejunal strips showed that CGRP reduced alanine absorption in a dose-dependent manner. At 6 pM, CGRP decreased alanine absorption by 33%. Similarly, CGRP reduced the absorption of proline and taurine by 20 and 11.5%, respectively. Kinetic studies revealed that CGRP reduces alanine influx into intestinal epithelial cells by inhibiting the affinity of the carriers. It is demonstrated that CGRP is involved in the regulation of jejunal amino acid absorption through intrinsic (enteric) and extrinsic (central) neural mechanisms.

Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats.

OBJECTIVE: To study the effect of the nitric oxide donor, molsidomine, on gastric and duodenal injury induced by indomethacin and aspirin. METHODS: Sprague-Dawley rats weighing 180-200 g were used after 24 h fasting. Indomethacin (5 mg/kg) was given subcutaneously as a single dose and followed by multiple injections of histamine. Molsidomine (0.05 mg/kg) or distilled water was given by gavage 30 min before indomethacin and repeated at 3 h intervals for two doses. Rats were killed 2 h after the last dose of molsidomine. Aspirin (500 mg/kg) was given by gavage and repeated 2.5 h later. Molsidomine or distilled water was given 30 min before the initial aspirin dose and repeated after 2 h. Animals were killed 2.5 h after the second dose of aspirin. The severity of the gastric mucosal damage was graded from 0 to 3, and the duodenal bulb ulcer surface area calculated by two independent observers using a dissecting microscope. RESULTS: Indomethacin and aspirin resulted in significant gastric mucosal damage with median scores of 2 (interquartile ranges 1.4-3, n = 16 and 2-3, n = 10, respectively). Molsidomine significantly ameliorated indomethacin- and aspirin-induced damage with median scores of 1 (interquartile ranges 0.5-1.5, n = 19 and 0.6-1.9, n = 10, respectively; P<0.008 and P<0.02, respectively (Mann-Whitney Utest)). Molsidomine had no effect on duodenal bulb ulcerations caused by indomethacin. CONCLUSION: Oral molsidomine has a protective effect on gastric mucosa against damage induced by ulcerogenic agents. This could have an important clinical benefit, especially in cardiac patients taking aspirin in addition to a nitric oxide donor such as molsidomine.

Reversal of impaired calcium homeostasis in the rat diaphragm subjected to Monocrotaline-induced pulmonary hypertension.

Monocrotaline (MCT) pneumotoxicity is known to alter the structure of pulmonary vascular wall and impairs endothelial cell function resulting in pulmonary hypertension. Its effect on the diaphragm muscle has not yet been elucidated. This study examines the effect of MCT pneumotoxicity on calcium transport in the rat diaphragm. Pulmonary hypertension induced by MCT pneumotoxicity caused a significant increase (P < 0.001) in calcium accumulation in strips isolated from rat diaphragms. Treatment of rats having received MCT with Indapamide reduced calcium uptake by diaphragmatic strips to levels that are not significantly different from the control (P > 0.05). Treatment with Indapamide alone did not elicit any change in calcium accumulation in the diaphragmatic strips. Treatment of the animals with MCT, Indapamide or both did not produce any significant change (P > 0.05) in the cell volume of the diaphragmatic strips. Pulmonary hypertension increased calcium uptake by the muscle cells in the rat diaphragm which may alter diaphragmatic contractility; an effect that was prevented by Indapamide.

Neural mediation of vasoactive intestinal polypeptide inhibitory effect on jejunal alanine absorption.

It was recently shown that vasoactive intestinal polypeptide (VIP) inhibits rat jejunal alanine absorption, an effect that was significantly reduced by vagotomy. This study assesses the role of capsaicin-sensitive primary afferents (CSPA) and the myenteric plexus in the inhibition of rat jejunal alanine absorption by VIP. Continuous intravenous infusion of VIP (11.2 ng . kg-1 . min-1) reduced alanine absorption by 60% in sham control rats and by 20% in rats neonatally treated with capsaicin (P < 0.01). In in vitro experiments, VIP decreased alanine uptake by jejunal strips isolated from sham control rats in a dose-dependent manner. In the presence of 40 nM VIP, alanine uptake by full-thickness jejunal strips was reduced by 54% in sham control rats and by 25% in rats neonatally treated with capsaicin (P < 0.001). On the other hand, VIP reduced alanine uptake by mucosal scrapings by 25% in sham rats compared with 9% reduction in neonatally treated rats. Chemical ablation of the extrinsic innervation and jejunal myenteric plexuses by pretreatment with benzalkonium chloride significantly (P < 0.001) reduced basal alanine absorption and the inhibitory effect of VIP. Moreover, incubation of intestinal strips with tetrodotoxin and atropine reduced significantly (P < 0.05) the inhibitory effect of VIP on alanine absorption. These data suggest that VIP exerts its inhibitory effect on alanine absorption through the CSPA fibers and the myenteric plexus. The neuronal circuitry of this inhibitory process may involve cholinergic muscarinic mechanisms.

Effects of capsaicin and capsaicin desensitization on alanine accumulation in rat hemidiaphragms.

1. Alanine accumulation in rat hemidiaphragms is significantly inhibited by capsaicin in a dose-dependent pattern that produced maximal effect at 1 mM. 2. The inhibitory effect of capsaicin on alanine accumulation by rat hemidiaphragms was enhanced upon preincubation with 5 mM ouabain. However, preincubation with 1 mM Verapamil did not alter the inhibitory effect of capsaicin. 3. Chemical ablation of the capsaicin-sensitive primary afferent fibers abolished the inhibitory effect of capsaicin on alanine accumulation in the rat hemidiaphragms.

Head trauma: CT scan interpretation by radiology residents versus staff radiologists.

PURPOSE: To determine the rate and clinical outcome of discrepancies in interpretation by radiology residents and staff neuroradiologists of posttraumatic cranial computed tomographic (CT) scans. MATERIALS AND METHODS: Prospective evaluation was performed for 419 consecutive emergency posttraumatic cranial CT studies that had been interpreted by radiology residents on call over a 16-month period. Discrepancies between the interpretations made by residents and those made by staff radiologists were divided into two groups: failure to recognize an abnormality (false-negative finding) and interpretation of normal as abnormal (false-positive finding). Discrepancies were considered major if they could affect patient care in the emergency setting and minor if they could not. RESULTS: Major and minor discrepancies were 1.7% and 2.6%, respectively, among interpretations made by residents and those by staff radiologists. Major discrepancies were four subdural hematomas, one pneumocephalus, one hemorrhagic contusion, and one subarachnoid hemorrhage. Minor discrepancies included six skull and five facial fractures. The discrepancy rate was statistically significantly higher (12.2%) when CT findings were abnormal than when they were normal (1.5%). No change in treatment was attributed to the delay in diagnosis. CONCLUSION: A low discrepancy rate was found between interpretations made by radiology residents and those made by staff neuroradiologists of posttraumatic cranial CT scans. There were no adverse clinical outcomes.

Age influence on intestinal taurine transport in mice.

Taurine plays a role in neurologic development and neuromuscular function. The high need for taurine during development, and the low capacity for endogenous biosynthesis make its intestinal handling very important. In this in vitro study, we investigated the uptake of taurine by intestinal strips obtained from adult, 10-day and 20-day-old mice. Intestinal strips from adult, 10-day and 20-day-old mice accumulated taurine against a concentration gradient. Moreover, the capacity of the intestinal cells to concentrate taurine decreased with age. A major component of the transport process was carrier-mediated and Na-dependent. Analysis of the kinetics of taurine uptake revealed that Vmax decreased as the animals grow older without a significant change in apparent Kt. It is concluded that as mice grow older their intestinal capacity to absorb taurine decreases.