Biomedical subjects

A R Dehpour

Publications and source records attributed to A R Dehpour.

At least 19 recordsLinked to original sources

PubMed2006

Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors.

BACKGROUND AND PURPOSE: Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist), AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was assessed by western blot and RT-PCR. KEY RESULTS: Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group. CONCLUSIONS AND IMPLICATIONS: These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms.

Animals↗

PubMed2006

Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats.

AIM: The aim of this study was to investigate the hypothesis that the opioid system is involved in the development of hepatic fibrosis. METHODS: The effect of naltrexone (an opioid receptor antagonist) on hepatic fibrosis in bile duct ligated (BDL) or sham rats was assessed by histology and hepatic hydroxyproline levels. Liver matrix metalloproteinase 2 (MMP-2) was measured by zymography, and alpha smooth muscle actin (alpha-SMA) and CD45 (leucocyte common antigen) by immunohistochemistry. The redox state of the liver was assessed by hepatic glutathione (GSH)/oxidised glutathione (GSSG) and S-nitrosothiol levels. Subtypes of opioid receptors in cultured hepatic stellate cells (HSCs) were characterised by reverse transcriptase-polymerase chain reaction, and the effects of selective delta opioid receptor agonists on cellular proliferation, tissue inhibitor of metalloproteinase 1 (TIMP-1), and procollagen I expression in HSCs determined. RESULTS: Naltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p<0.01), and decreased the number of activated HSCs in BDL rats (p<0.05). The development of biliary cirrhosis altered the redox state with a decreased hepatic GSH/GSSG ratio and increased concentrations of hepatic S-nitrosothiols, which were partially or completely normalised by treatment with naltrexone, respectively. Activated rat HSCs exhibited expression of delta1 receptors, with increased procollagen I expression, and increased TIMP-1 expression in response to delta(1) and delta(2) agonists, respectively. CONCLUSIONS: This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.

Animals↗

PubMed2006

High sensitivity of chicken's skeletal muscle sarcoplasmatic reticulum to effects of diltiazem or verapamil on calcium uptake and release.

In this study, the effects of two different calcium channel blockers, diltiazem and verapamil on calcium uptake and release from the membrane of heavy sarcoplasmic reticulum (SR) of chicken skeletal muscle were investigated. A fluorescent chelate probe technique was employed to determine calcium movement through the SR. Chlortetracycline was used as a fluorescent indicator which is able to penetrate the membrane, bind to the calcium on the inner face of the membrane and show an increase in fluorescence intensity when calcium uptake occurs. Addition of tris-ATP to the microsomes caused ATP-induced calcium uptake in a concentration dependent manner with half-maximal calcium uptake around 0.126 mM. Pretreatment of the medium containing sarcoplasmic reticulum with different concentrations of diltiazem or verapamil followed by added tris-ATP resulted a significant decrease in the fluorescence intensity of chlortetracycline, showing that these calcium channel blockers can diminish ATP-induced calcium uptake in a concentration-dependent manner. The maximum fluorescence intensity of tris-ATP falls to 50% in the presence of 1.75 microM diltiazem and 25 nM verapamil. In addition, diltiazem and verapamil can significantly induce rapid calcium release from the membrane of sarcoplasmic reticulum in a concentration-dependent manner. Therefore, membrane-bound or sequestered calcium in the sarcoplasmic reticulum may be targeted by these two calcium channel blockers in chicken skeletal muscle. Chicken SR is about 1000 times more sensitive to the effects of diltiazem on Ca2+ uptake and release than rabbit SR as shown previously.

Adenosine Triphosphate↗

PubMed2005

Diethyl methyl chitosan as an intestinal paracellular enhancer: ex vivo and in vivo studies.

Chitosan exhibits favorable biological properties such as no toxicity, biocompatibility and biodegradability; therefore, it has attracted great attention in both pharmaceutical and biomedical fields. Chitosan exhibits poor solubility at pH values above 6 that prevents enhancing effects at the sites of absorption of drugs. In the present work, N-diethyl methyl chitosan (DEMC) was prepared and the enhancing effect of this polymer was investigated. Ex vivo studies have shown a significant increase in absorption of brilliant blue in the presence of diethyl methyl chitosan in comparison with chitosan. DEMC with positive charges is able to interact with tight junctions of colon epithelial cells and hence increases permeability of brilliant blue across the tight junctions. In vivo investigations have exhibited the absorption enhancer effects of DEMC on the colon absorption of insulin in normal and diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect. A significant decrease in blood glucose was observed, when mixture of insulin and DEMC was introduced in ascending colon of rats.

Animals↗

PubMed2005

Preconditioning of the rat random-pattern skin flap: modulation by opioids.

Opioid receptors have been implicated in protecting several organ systems from ischaemic events. The authors have studied the effects of opioid receptors on random-pattern skin flap survival. Sixty-nine male Sprague-Dawley rats were used. Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. Different doses of morphine (0.01, 0.1, 1 and 5 mg/flap) were administered locally in the cranial half of the flap and systemically through intraperitoneal injections (5 and 10 mg/kg). In another experiment, 0.4 mg/flap of naloxone was injected followed by 5 mg/flap injection of morphine to determine whether the effect of morphine is receptor mediated. The role of the opioid receptors in the ischaemic preconditioning (IPC) phenomenon was investigated by administration of naloxone (0.4 mg/flap) 1 h before clamping the cranial pedicle for 20 min followed by 40 min of reperfusion. Appropriate control groups were included. The cranial pedicle was cut 2 h after saline or drug administration in all groups and flap survival area was evaluated on the seventh postoperative day. Local administration of morphine in higher doses (1 and 5 mg/flap) significantly reduced the amount of flap necrosis when compared to that of the control cohort (P < 0.05). Naloxone abolished this protective effect of morphine. Furthermore naloxone significantly decreased the anti-ischaemic effect of the IPC. Systemic administrations of morphine had no significant effect on flap survival area in compare with the control group.

Animals↗

PubMed2005

Enhancement of indomethacin-induced gastric damage by mouth breathing in rabbits.

Previous studies have reported that mouth breathing is associated with respiratory acidosis. Regarding to the reports that renal elimination of weak acids such as indomethacin is pH dependent, this study was carried out to evaluate the role of mouth breathing on plasma level of indomethacin and indomethacin-induced gastric damage in rabbits. Mouth breathing was induced by surgical ligation of nostrils under general anesthesia. One day after the operation, arterial blood samples were collected for acid-base balance analysis and indomethacin was administered intraperitoneally in a single dose of 40mg/kg. The animals were killed 4h after indomethacin administration and blood samples were collected for spectrofluorometric determination of indomethacin in plasma. The results showed that indomethacin induces more severe gastric damage in nose obstructed rabbits compared with sham and unoperated (UNOP) animals. Acid-base analysis revealed a respiratory acidosis in nose obstructed rabbits and indomethacin level of plasma was significantly higher in nose obstructed animals in comparison with control rabbits. The study shows that mouth breathing can increase the potentiation of indomethacin-induced gastric mucosal damage that may be due to higher level of indomethacin in plasma of nose obstructed animals.

Journal Article↗

PubMed2005

Densitometric evaluation of skull and jaw bones after administration of thyroid hormones in rats.

OBJECTIVES: An investigation was performed by use of optical densitometry to observe the effects of different doses of thyroid hormone on bone density of skull and jaw bones and to evaluate the relationship between T3, T4, thyroid stimulating hormone (TSH) serum levels and bone density. METHODS: 40 Sprague-Dawley rats were randomly divided into four groups with 10 rats in each (a control group that received 10 ml kg(-1) i.p. per day normal saline and three levothyroxine groups that received 5, 10, or 20 microg kg(-1) i.p. per day levothyroxine, respectively). Radiographs were taken of their skulls on days 3 and 16. At the end of the experimental period blood was drawn by intracardiac puncture and serum was analysed for thyroid hormones (T3 and T4) and TSH level. After that, optical density measurements were made on the radiographs of four selected points on the skull and jaw with a digital densitometer. Density measurements were analysed using the student's t-test, one way analysis of variance, Spearman correlation analysis and regression analysis. RESULTS: Levothyroxine administration reduced bone density (P < or = 0.05) and increasing the dose of thyroid hormone produced a significant decrease of bone density (P < or = 0.05). The mandible was more susceptible to density changes compared with hard palate, skull and alveolar bone (P < or = 0.05). CONCLUSIONS: Radiographs of the mandible can be utilized to characterize loss of bone density elsewhere. In addition this investigation indicated that optical densitometry is an inexpensive and low risk method for studying bone density.

Absorptiometry, Photon↗

PubMed2004

Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.

Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. Systemic administration of ultra-low doses of naltrexone (100 fg/kg-10 ng/kg) significantly potentiated the anticonvulsant effect of morphine at 0.5 mg/kg while higher degrees of opioid receptor antagonism blocked this effect. Moreover, inhibition of opioid-induced excitatory signaling by naltrexone (1 ng/kg) unmasked a strong anticonvulsant effect for very low doses of morphine (1 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of opioid receptor signaling can exert strong seizure-protective effects even at very low levels of opioid receptor activation. However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.

Animals↗

PubMed2003

Relationship between erythrocyte lithium concentration and renal concentrating capacity.

BACKGROUND: Studies investigating possible correlations between plasma lithium concentration, lithium treatment duration, and frequency of lithium administration, and lithium nephrotoxicity have yielded conflicting results. OBJECTIVES: Our main objective was to investigate whether there was any relationship between erythrocyte lithium concentration (ELC) and renal side effects. Another objective of our study was to identify a parameter, which could be estimated inexpensively, for assessing possible renal side-effects of lithium. METHOD: Seventy Iranian inpatients with bipolar disorder entered this case-control study. Medications taken concurrently by the patients were recorded. A direct method of measuring ELC was used in this study. The cases were patients on lithium who had urine specific gravity (SG) of 1.006 or less after 8-10 h water deprivation at night and the controls consisted of patients on lithium with urine SG of 1.011 or more after this period. Blood urea nitrogen, serum creatinine, sodium and potassium and urine SG, sodium, and potassium were measured in all patients during this time. Renal indices were compared by using independent sample t-test at a significance level of a P-value of 0.05 or less. Non-parametric Spearman's rank correlation test was used to investigate the relationship between clinical variables and the indices of renal function. RESULTS: Results revealed that in case group mean serum sodium concentrations were significantly higher (P = 0.008) and mean urine sodium and potassium were significantly lower than those of controls (P = 0.004 and 0.007 respectively). We found no statistically difference in lithium ratios between the two groups. However, ELCs were significantly higher in the cases (P = 0.026). There were no significant correlation between concomitant use of neuroleptics, benzodiazepines or carbamazepine and ELC or lithium renal side-effects. CONCLUSION: This study showed that ELC may reflect lithium renal side-effects better than plasma lithium level.

Adult↗

PubMed2003

Alpha 2-adrenoceptor and NO mediate the opioid subsensitivity in isolated tissues of cholestatic animals.

1. Our previous report showed that in acute cholestasis, the subsensitivity to morphine inhibitory effect on electrical-stimulated contractions develops significantly faster in guinea-pig ileum (GPI) and in mouse vas deferens (MVD) (45.2 and 29.9 times, respectively) compared with non-cholestatic subjects. 2. The possible contribution of alpha2-adrenoceptor and nitric oxide (NO) pathways on the development of tolerance was assessed in GPI and MVD of cholestatic subjects. 3. Daily administration of naltrexone (20 mg kg(-1)), yohimbine (5 mg kg(-1)), and Nomega-nitro-l-arginine methyl ester (l-NAME) (3 mg kg(-1)) to cholestatic animals significantly (P-value < 0.05) inhibited the process of subsensitivity in all groups. 4. Consistent with the literature, it was concluded that both the alpha2-adrenergic system and NO have close interaction with the opioid system and may underlie some of the mechanisms involved in the subsensitivity development to opioids in acute cholestatic states.

Analgesics, Opioid↗

PubMed2003

The effects of FK506 on the development and expression of morphine tolerance and dependence in mice.

FK506 is an immunophilin-binding ligand that inhibits calcineurin and decreases nitric oxide (NO) production in the nervous tissues. We examined the effects in mice of systemic treatment with FK506 on the induction and expression of morphine (s.c.) tolerance and dependence and compared them with the effects of the non-specific NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and specific inducible NO synthase inhibitor, aminoguanidine. FK506 (0.5-10 mg/kg, s.c.) exerted inhibitory effects on both development and expression of tolerance to morphine-induced antinociception. FK506 also significantly decreased the expression of morphine dependence, as assessed by naloxone-precipitated (2 mg/kg, i.p.) withdrawal syndrome, but a similar effect was not found for the development of morphine dependence. A similar pattern of effects was observed with L-NAME (3-20 mg/kg, i.p.), while aminoguanidine (50-100 mg/kg, i.p.) did not alter tolerance or dependence. Examining the possible interaction between their inhibitory effects on tolerance and dependence, we combined the subeffective doses of FK506 (0.5 or 1 mg/kg) with L-NAME (3 mg/kg) or aminoguanidine (100 mg/kg). The combination of FK506 with L-NAME, but not with aminoguanidine, significantly decreased the development and expression of tolerance and expression of dependence. These data show the effectiveness of FK506 on morphine tolerance and dependence and suggest an additive effect between FK506 and the inhibition of constitutive NO synthesis in this regard.

Analgesics↗

PubMed2001

Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid and nitric oxide systems.

Changes in vascular responsiveness are proposed as the basis for some of the cardiovascular complications in cholestasis. Cholestasis is also associated with accumulation of endogenous opioid peptides and evidence of overproduction of nitric oxide (NO). The possible role of NO or opioid system in cholestasis-induced mesenteric vascular bed responsiveness was investigated. Bile duct-ligated and sham-operated rats were treated for 6 days with either normal saline, naltrexone, an opioid antagonist (20 mg/kg/day) or L-NAME (N(omega)-nitro-L-arginine methyl ester), a nitric oxide synthase inhibitor (3 mg/kg/day). After 7 days, the superior mesenteric artery was cannulated and the mesenteric vascular bed was perfused according to the McGregor method. Baseline perfusion pressure of the mesenteric vascular bed was decreased in bile duct-ligated compared to sham-operated animals. ED(50) of phenylephrine-induced vasoconstriction was increased, but vasoconstriction R(max) was not different in the vascular bed of bile duct-ligated rats and of sham-operated ones. Acetylcholine-induced vasorelaxation was impaired in bile duct-ligated rats (increased ED(50) and decreased vasorelaxation R(max)). Sodium nitroprusside-induced vasorelaxation was not different between bile duct-ligated and sham-operated rats, implying that the smooth muscle components of vasorelaxation were intact. Chronic treatment with L-NAME partially restored both the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction response in bile duct-ligated rats. Naltrexone treatment also partially restored the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in bile duct-ligated rats. There is impaired acetylcholine-induced vasorelaxation in cholestatic rats, probably due to a defect in endothelial function. This study also provided evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced vascular hyporesponsiveness.

Acetylcholine↗

PubMed2001

The role of nitric oxide in bradycardia of rats with obstructive cholestasis.

Nitric oxide (NO) has an important role in controlling heart rate and contributes to the cholinergic antagonism of the positive chronotropic response to adrenergic stimulation. Based on evidence of NO overproduction in cholestasis and also on the existence of bradycardia in cholestatic subjects, this study aimed to evaluate the chronotropic effect of epinephrine in isolated atria of cholestatic rats and determine whether alterations in epinephrine-induced chronotropic responses of cholestatic rats are corrected after systemic inhibition of NO synthase (NOS) with N(G)-nitro-L-arginine (L-NNA). Male Sprague-Dawley rats were used. Cholestasis was induced by surgical ligation of the bile duct under general anesthesia and sham-operated animals were considered as control. The animals were divided into three groups, which received either L-arginine (200 mg/kg/day), L-NNA (10 mg/kg/day) or saline. One week after the operation, a lead II ECG was recorded from the animals, then spontaneously beating atria were isolated and chronotropic responses to epinephrine were evaluated in a standard oxygenated organ bath. The results showed that plasma gamma-glutamyl transpeptidase and alanine aminotransferase activity was increased by bile-duct ligation, and that L-aginine treatment partially, but significantly, prevented the elevation of these markers of liver damage. The results showed that heart rate of cholestatic animals was significantly less than that of sham-operated control rats in vivo and this bradycardia was corrected with daily administration of L-NNA. The basal spontaneous beating rate of atria in cholestatic animals was not significantly different from that of sham-operated rats in vitro. Meanwhile, cholestasis induced a significant decrease in chronotropic effect of epinephrine. These effects were corrected by daily administration of L-NNA. Surprisingly L-arginine was as effective as L-NNA and increased the chronotropic effect of epinephrine in cholestatic rats but not in sham-operated animals. Systemic NOS inhibition corrected the decreased chronotropic response to adrenergic stimulation in cholestatic rats, and suggests an important role for NO in the pathophysiology of heart rate complications in cholestatic subjects. The opposite effect of chronic L-arginine administration in cholestasis and in control rats could be explained theoretically by an amelioration of cholestasis-induced liver damage by chronic L-arginine administration in bile duct-ligated rats.

Alanine Transaminase↗

PubMed2001

Time-dependent reduction of acetylcholine-induced relaxation in aortic rings of cholestatic rats.

Changes in vascular responsiveness are the basis for some of the cardiovascular complications in cholestasis. Since the duration of cholestasis is important in determining the degree of the complications, we investigated the time-course dependent evolution of vascular relaxation responsiveness in the aortic rings of cholestatic rats. Acetylcholine-induced endothelium-dependent relaxation was investigated in the isolated aortic rings of unoperated, sham-operated and two-, five-, seven- and fourteen-day bile-duct ligated rats. There was a significant reduction in acetylcholine-induced relaxation of the aortic rings by the second day after the bile-duct ligation operation, compared to those of unoperated and sham-operated groups, but more reduction still occurs in 5- and 7-day bile-duct ligated groups, reaching a plateau by the seventh day. The relaxation response to sodium nitroprusside in the aortic rings of the unoperated and the 7-day bile-duct ligated rats did not differ, implying the intact smooth muscle component of the relaxation pathway. L-NAME ( N(omega)-nitro-L-arginine methyl ester), a nitric oxide (NO) synthase inhibitor, attenuated the acetylcholine-induced relaxation in both groups (unoperated and bile-duct ligated), while L-arginine prevents this inhibitory effect. Indomethacin potentiated the acetylcholine-induced relaxation in the aortic rings of the bile-duct ligated rats while it has no effect on unoperated controls, providing evidence for the possible role of vasoconstrictor prostanoids in cholestasis-induced reduction in acetylcholine-induced relaxation. These results state that the reduced acetylcholine-induced relaxation in the cholestatic aortic rings during the first week, when no portal hypertension was reported to be present, may be due to the decreased acetylcholine-induced NO release from endothelium or increased NO inactivation.

Acetylcholine↗

PubMed2001

Clonidine attenuates naloxone-induced opioid-withdrawal syndrome in cholestatic mice.

Cholestasis is associated with elevated plasma level of endogenous opioid peptides. Naloxone-precipitated withdrawal syndrome has been described in a mouse model of acute cholestasis. Thus we aimed at determining whether central noradrenergic hyperactivity is involved in manifestation of naloxone-precipitated withdrawal syndrome in mice with obstructive cholestasis. Acute cholestasis was induced by bile duct resection in mice and physical dependence was observed by precipitating a withdrawal syndrome with naloxone (2 mg/kg, intraperitoneally) 5 days after induction of cholestasis. Administration of clonidine (0.1 mg/kg, intraperitoneally), an alpha2-adrenoceptor agonist, 15 min. before naloxone injection significantly alleviates withdrawal severity in cholestatic mice. However, pretreatment of animals with yohimbine (3 mg/kg, intraperitoneally), an alpha2-adrenoceptor antagonist, 15 min. before clonidine blocked this ameliorative effect of clonidine. The results of this study support the evidence for involvement of the alpha2-adrenoceptors in the withdrawal syndrome of cholestasis in a mouse model.

Adrenergic alpha-Agonists↗

PubMed2001

The effect of chronic renal insufficiency on orthodontic tooth movement in rats.

The purpose of this study was to determine the effects of impaired renal function on the amount of orthodontic tooth movement (OTM) in a rat model of renal insufficiency (RI). The animals were divided into three groups: a control unoperated group in which only OTM was done, a sham-operated group, and an RI group. OTM was done two weeks after performance of the sham operation or the surgery to induce RI. Renal failure was induced by electrocoagulation of one kidney cortex followed by contralateral nephrectomy. A fixed orthodontic appliance consisting of a 5 mm length of nickel-titanium closed-coil spring was ligated between the maxillary right incisor and first molar to deliver an initial mesial force of 60 g. Four weeks after RI induction, the amount of tooth movement was estimated by measuring the space created between the first and second molars on a stone cast. Bone density was measured by optical densitometry on radiographs and serum parathyroid hormone (PTH) was measured with a radioimmunoassay method. The results showed that induction of RI significantly increased both OTM (P < .05) and PTH levels (P < .01), although there was no significant difference in bone density by optical densitometry between the unoperated, sham-operated, and RI groups four weeks after RI induction. The results suggest that an increase of bone-remodeling activities, as evident from a significantly higher level of PTH, may be responsible for increase in tooth movement.

Analysis of Variance↗

PubMed2001

The role of the interaction between endogenous opioids and nitric oxide in the pathophysiology of ethanol-induced gastric damage in cholestatic rats.

Interaction between endogenous opioids and nitric oxide (NO) has been shown in different biological models and pharmacological evidence suggest that opioids can induce NO release in endothelium as well as in neural cells. Cholestasis is associated with NO overproduction. The reason for increased NO synthesis is not clearly known but it can potentiate development of gastric mucosal damage in cholestatic subjects. Based on increased plasma levels of endogenous opioids and existence of NO overproduction in cholestasis, the present experiments were performed to investigate the role of interaction between endogenous opioids and NO in generation of ethanol-induced gastric damage in cholestatic rats. Cholestasis was induced by surgical ligation of bile duct and sham-operated rats served as controls. The animals received either 20 mg/kg of naltrexone or saline for 6 days and then were fasted and received L-arginine (200 mg/kg), NG-nitro-L-arginine methylester (L-NAME; 2, 5 and 10 mg/kg) or saline. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than in sham-operated animals (115 +/- 12 mm2 vs. 72 +/- 11 mm2, P < 0.05). L-NAME significantly enhanced the development of gastric mucosal lesions in sham-operated rats. But in cholestatic animals, L-NAME decreased and L-arginine enhanced the severity of gastric damage. Pretreatment of animals with naltrexone decreased severity of gastric mucosal damage in cholestatic rats. Concurrent administration of naltrexone with L-arginine was protective against ethanol-induced gastric damage in both normal and cholestatic groups. Administration of naltrexone with L-NAME had the same effect in cholestatic and control rats and increased severity of gastric damage. Plasma levels of NO2- + NO3- were significantly higher in cholestatic rats than control animals (72 +/- 6 microM vs. 39 +/- 3 microM, P < 0.05). Pretreatment of animals with naltrexone significantly reduced plasma levels of NO2- + NO3- in cholestatic animals, but not in control rats (33 +/- 6 microM vs. 32 +/- 4 microM). The protective effect of L-NAME against gastric damage in cholestatic rats can be explained by inhibition of NO overproduction and it seems that interaction between opioids and NO may have an important role in generation of NO overproduction and gastric complications in cholestatic rats.

Alcohol Deterrents↗

PubMed2001

Inhibition of serum angiotensin-converting enzyme in rabbits after intravenous administration of enalaprilat-loaded intact erythrocytes.

Encapsulation of drugs in intact erythrocytes, because of the profound characteristics of these natural microspheres, has gained considerable attention in recent years. In this study, the inhibition time courses of serum angiotensin-converting enzyme (ACE) activity after intravenous administration of enalaprilat encapsulated in intact erythrocytes was evaluated and compared with free drug, in a rabbit model. Three groups of animals each received free drug, drug-loaded erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined in each case using the synthetic substrate hippuryl-histidyl-leucine and quantitation of the hippuric acid released by a developed and validated HPLC method. The serum ACE inhibition profiles in the three groups showed that the encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a considerably longer time and in a more reproducible manner, than the free drug or sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as efficacious slow-release drug carriers for enalaprilat in circulation.

Angiotensin-Converting Enzyme Inhibitors↗