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Biomedical subjects

S Taheri

Publications and source records attributed to S Taheri.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prolactin releasing peptide (PrRP) stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) via a hypothalamic mechanism in male rats.

Prolactin releasing peptide (PrRP) was originally isolated as an endogenous hypothalamic ligand for the hGR3 orphan receptor. It has been shown to release prolactin from dispersed pituitaries harvested from lactating female rats and only at very high doses in cycling females. PrRP is reported to have no effect on prolactin production from dispersed pituitary cells harvested from males. The CNS distribution of this peptide suggested a role for PrRP in the control of the hypothalamo-pituitary axis. The aim of this study was to examine the actions of PrRP (1-31) on circulating pituitary hormones following intracerebroventricular (ICV) injection in male rats and to investigate the mechanism of PrRP's effect by measurement of hypothalamic releasing factors in vitro. In our experiments, PrRP (1-31) did not release LH, FSH, TSH, growth hormone or prolactin directly from dispersed male pituitary cells in vitro. We have shown for the first time that following ICV injection of PrRP (1-31) 5 nmol there was a highly significant simulation of plasma LH that began at 10 minutes and was maintained over the course of the experiment (at 60 minutes PrRP 5 nmol 2.2 +/- 0.2 vs. saline 0.5 +/- 0.1 ng/ml, p<0.001). Plasma FSH increased at 20 minutes following ICV injection (PrRP 5nmol 10.8 +/- 2.0 ng/ml vs. saline 5.1 +/- 0.5, p<0.01). Total plasma testosterone increased at 60 minutes post injection (PrRP 5nmol 9.2 +/- 1.6 vs. saline 3.5 +/- 0.6 nmol/l, p<0.01). There was no significant alteration in plasma prolactin levels. PrRP significantly increased the release of LHRH from hypothalamic explants in vitro (PrRP 100nmol/l 180.5 +/- 34.5% of the basal secretion, p<0.05). PrRP (100nmol/l) also increased the following hypothalamic peptides involved in the control of pituitary hormone release, vasoactive intestinal peptide (VIP) 188.1 +/- 24.6% and galanin 153.8 +/- 13.0% (both p<0.001 vs. basal secretion) but had no effect on orexin A secretion. These results suggest a role for PrRP in the control of gonadotrophin secretion acting via a hypothalamic mechanism involving the release of LHRH.

Animals↗
PubMed2000

Islet cell tumours: diagnosis and medical management.

Islet cell tumours are difficult to diagnose. They are rare tumours that secrete hormones resulting in symptoms and signs that are often mistaken for more common conditions. Benign and solitary tumours are surgically resected, while medical therapy aims at symptom control and palliation of malignant disease.

Adenoma, Islet Cell↗
PubMed2000

Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

Animals↗
PubMed1999

Distribution and quantification of immunoreactive orexin A in rat tissues.

A sensitive and specific radioimmunoassay for orexin A was developed. Orexin A immunoreactivity was found to be confined to the central nervous system (CNS) with the highest concentrations in the hypothalamus, inferior and superior colliculi and brainstem. Within the hypothalamus, the highest levels were found in the lateral and posterior hypothalamus. These regions had a greater orexin A content in females compared to males. The orexin A content of hypothalamic regions did not change with fasting and no difference was noted in hypothalami of rats fed a high fat diet. The hypothalamic orexin A content was not different in obese Zucker rats compared to lean controls. Thus, orexin A has a wide distribution in the CNS, but appetite regulation may not be its main function.

Animals↗
PubMed1999

A multicenter, phase I evaluation of cryopreserved venous valve allografts for the treatment of chronic deep venous insufficiency.

PURPOSE: A phase I feasibility study was conducted to determine whether cryopreserved venous valved segments would remain patent/competent in a short-term period (6 months). METHODS: The target group consisted of 10 patients (C(4-6), E, A(D), P(R)). The exclusion criteria included untreated superficial/perforator venous disease, significant venous or arterial obstruction, hypercoagulability or coagulopathy, and significant preexisting medical conditions. Required preoperative tests were venous duplex, ascending/descending venography, and a physiologic study (eg, APG, blood typing, an ankle/brachial index, and if post-thrombotic, a hypercoagulability work-up). A single-valve transplant was placed below all reflux, aided by anticoagulation with or without a distal arteriovenous fistula. Postoperative assessment included duplex scanning/clinical examination (at 1, 3, and 6 months), descending venogram (at 1 month), and physiologic study (at 1 and 6 months). The primary end point was valve patency/competence, with clinical outcome as a secondary end point. Adverse events were recorded. RESULTS: After eliminating protocol violations, nine patients with superficial femoral (5) or popliteal (4) vein valve transplants were studied. Six-month actuarial results show a patency rate of 67% +/- 16% and 78% +/- 13%, respectively, a primary and secondary competency rate of 56% +/- 17% and 67% +/- 16%, respectively, and a 100% patient survival rate. Clinical outcome averaged 1.1, with healing and/or freedom from ulcer recurrence, in six of nine patients. A postoperative risk of seroma formation (3) and cellulitis (1) exists. CONCLUSION: In patients with few remaining therapeutic options, one can achieve a 6-month assisted patency and competency rate of 78% and 67%, respectively, with an improved clinical outcome.

Actuarial Analysis↗
PubMed1999

A demonstration of the concentration and second gas effects in humans anesthetized with nitrous oxide and desflurane.

UNLABELLED: In the present study, we explored both the existence of and the basis for the concentration and second gas effects. Groups of six normocapnic patients were given one of three gas mixtures via a nonrebreathing system: 65% nitrous oxide (N2O) plus 4% desflurane; 5% N2O plus 4% desflurane; or 65% N2O plus 0.5% desflurane plus 2% xenon (Xe). End-tidal carbon dioxide (CO2) was held constant by adjustments in ventilation. Confirming the existence of the concentration effect, the end-tidal (F(A)) concentration of N2O increased toward the inspired (F(I)) concentration more rapidly (i.e., F(A)/F(I) increased more rapidly) when the inspired concentration was 65% than when it was 5%. The F(A)/F(I) for desflurane also increased more rapidly when desflurane was given with 65% rather than 5% N2O, confirming the existence of the second gas effect. The small uptake of the second gas (desflurane) did not influence its own F(A)/F(I) or that of N2O; that is, the administration of 4%, rather than 0.5%, desflurane did not increase the rate of rise of F(A)/F(I) of either N2O or desflurane. One of the bases of the concentration and second gas effects, a concentrating of residual gases, was confirmed: administration of Xe with 65% N2O produced an F(A)/F(I) for Xe that exceeded 1.0. Patient sex did not seem to influence the rate of rise of F(A)/F(I) of either N2O or desflurane. Finally, we unexpectedly found that, despite an equal solubility in blood, the rise in F(A)/F(I) for N2O exceeded that for desflurane, perhaps because of differences in tissue solubilities and intertissue diffusion. IMPLICATIONS: As predicted by the concentration and second gas effects, increasing the inspired concentration of nitrous oxide accelerated its rate of rise and the rate of rise of concurrently administered desflurane in humans.

Adult↗
PubMed1994

Pharmacokinetics do not explain the absence of an anesthetic effect of perfluoropropane or perfluoropentane.

In conflict with the prediction of the Meyer-Overton hypothesis, perfluoropropane (C3F8) and perfluoropentane (C5F12) have no anesthetic effect in rats. To test whether this resulted from a failure of the inspired drugs to reach the brain, we determined the increase in partial pressures of C3F8 and C5F12 in the blood and brains of rats exposed to 0.65 ata of each drug. C3F8 and C5F12 blood/gas partition coefficients equaled 0.00125 +/- 0.00037 (mean +/- SD, n = 9) and 0.00277 +/- 0.00082 (n = 4), and brain/gas partition coefficients equaled 0.0119 +/- 0.0002 (n = 4) and 0.0229 +/- 0.0055 (n = 7), respectively. As a fraction of the inspired value (Pa/PI), the partial pressures of C3F8 and C5F12 in blood (Pa) were 0.99 +/- 0.12 and 0.69 +/- 0.19, respectively, 30 min after administration. The increases in cerebral (Pb) partial pressures of both drugs paralleled the arterial increases (Pb/PI = 0.85 +/- 0.02, and 1.05 +/- 0.03, respectively at 30 min), with C3F8 reaching a plateau at 2 h of 96% +/- 4% of the partial pressure of inspired gas. We conclude that failure of C3F8 and C5F12 to reach the brain does not account for the absence of an anesthetic effect of these compounds.

Anesthesia, Inhalation↗
PubMed1994

A cutoff in potency exists in the perfluoroalkanes.

Anesthetic potencies (minimum alveolar anesthetic concentration [MAC]) of perfluoroalkanes from perfluoromethane to perfluorooctane were assessed in male rats to determine whether a cutoff in anesthetic effect (i.e., an absence of any anesthetic effect) exists for the larger compounds in this series. Although hyperbaric measurements suggested a MAC of 38.9 +/- 6 atm (mean +/- SD) for CF4, this pressure was nearly identical to the lethal pressure of 41.1 +/- 5.8 atm. Hyperbaric studies of C2F6 caused death without causing anesthesia, the lethal pressure being 23.8 +/- 2.6 atm. Results from studies of additivity with desflurane suggested that the MAC of CF4 was 66.5 +/- 13.4 atm at an average CF4 test partial pressure of 17.7 +/- 4.0 atm (i.e., 17.7 atm of CF4 decreased the MAC of desflurane by 26.6%). Studies of additivity with desflurane, isoflurane, or halothane did not reveal an anesthetic effect of C2F6 at a pressure of 7.2 +/- 0.4 atm, or of larger perfluoroalkanes near to or at their saturated vapor pressures. We conclude that a cutoff in anesthetic potency for perfluoroalkanes exists between perfluoromethane and perfluoroethane.

Alkanes↗
PubMed1994

Molecular properties of the "ideal" inhaled anesthetic: studies of fluorinated methanes, ethanes, propanes, and butanes.

We examined 35 unfluorinated, partially fluorinated, and perfluorinated methanes, ethanes, propanes, and butanes to define those molecular properties that best correlated with optimum solubility (low) and potency (high). Limited additional data were obtained on longer-chained alkanes. Using standard techniques, we assessed anesthetic potency (minimum alveolar anesthetic concentration [MAC] in rats); vapor pressure; stability in soda lime; and solubility in saline, human blood, and oil. If nonflammability, stability, low solubility in blood, clinically useful vapor pressures, and potency permitting delivery of high concentrations of oxygen are essential components of an anesthetic that might supplant those presently available, our data indicate that such a drug would have three or four carbon atoms with single or dual hydrogenation of two carbons, especially terminal carbons. We conclude that: 1) smaller and larger molecules and lesser hydrogenation provide insufficient potency; 2) high vapor pressures of smaller molecules do not permit the use of variable bypass vaporizers; 3) greater hydrogenation enhances flammability, and complete hydrogenation decreases potency; 4) internal hydrogenation decreases stability; and 5) greater hydrogenation increases blood solubility.

Alkanes↗
PubMed1994

Effect of n-alkane kinetics in rats on potency estimations and the Meyer-Overton hypothesis.

Neither lipophilicity nor vapor pressure of larger n-alkanes appear to correlate with their anesthetizing partial pressures in inspired gas. Such results suggest that the Meyer-Overton hypothesis and Ferguson's rule may not apply to these compounds. An alternative explanation might be that a large difference in inspired-to-arterial partial pressure exists, i.e., that the inspired partial pressure misrepresents the effective partial pressure. To test this explanation, we investigated the kinetics of five consecutive even-numbered n-alkanes (C2H6 to C10H22) in rats. The ratio of end-tidal-to-inspired (PA/PI), arterial-to-end-tidal (Pa/PA), and arterial-to-inspired (Pa/PI) partial pressures decreased with increasing carbon chain length, consistent with our separate finding that blood solubility increased. Using Pa/PI and the minimum inspired concentration (MIC) obtained previously, we calculated the true effective potency, minimum alveolar anesthetic concentration (MAC); of these n-alkanes as (Pa/PI)(MIC). This markedly improved, but did not perfectly correct, the correlation of MAC with lipid solubility (the Meyer-Overton hypothesis) and vapor pressure (Ferguson's rule). A coefficient of variation of 76.7% was found for the product of MAC and the olive oil/gas partition coefficient. More importantly, the correlation of the logarithm of MAC and oil solubility had a slope of -0.724 (i.e., deviated from -1.0), whereas the slope for eight conventional anesthetics was -1.046 (approached-1.0). These data imply that olive oil does not adequately mimic the nature of the anesthetic site of action of n-alkanes.

Alkanes↗
PubMed1993

Anesthesia by n-alkanes not consistent with the Meyer-Overton hypothesis: determinations of the solubilities of alkanes in saline and various lipids.

Because deviations from the Meyer-Overton rule may provide insights into the attributes of the anesthetic site of action, we characterized the solubility of the n-alkanes in various hydrophobic solvents (n-tetradecane, olive oil, n-octanol, and lecithin) as well as saline using variations on standard techniques. Increasing alkane chain length correlated with a decrease in solubility in saline and an increase in solubility in the hydrophobic solvents. The product of solubility in the hydrophobic solvents x the partial pressure (in atmospheres) required to produce anesthesia (i.e., the Meyer-Overton rule) did not produce a constant for any one of these solvents. The means and standard deviations for the products were: tetradecane, 65 +/- 103; olive oil, 33 +/- 63; n-octanol, 64 +/- 129; and lecithin, 16 +/- 26. Thus, our data suggest that the n-alkanes (especially those longer than n-heptane) do not follow the Meyer-Overton rule.

Alkanes↗
PubMed1993

Is there a cutoff in anesthetic potency for the normal alkanes?

Vapor pressures and anesthetizing partial pressures in rats were measured for 10 consecutive normal alkanes, methane through decane. All produced anesthesia as defined by the absence of movement in response to either the application of a tail-clamp or electrical stimulation of the tail. The anesthetizing partial pressure was calculated as the average between the concentrations just permitting and preventing movement. Although nonane and decane did not provide anesthesia when given alone at their saturated vapor pressures, their anesthetic properties could be demonstrated by their ability to decrease the anesthetic requirement for isoflurane (i.e., their anesthetic potencies could be defined by studies of additivity). Anesthetic potency increased (from 9.9 atm for methane to 0.0142 atm for decane) and vapor pressure decreased (from 38.2 atm for ethane to 0.0028 atm for decane) with increasing chain length. The decrease in vapor pressure far exceeded the increase in potency. For nonane and decane, the ratio of the partial pressure required for anesthesia to the saturated vapor pressure was less than 1, being 0.48 and 0.19, respectively. We conclude that no cutoff phenomenon (i.e., no absence of anesthetic effect with longer chain alkanes) exists from n-methane to n-decane, but that larger alkanes have vapor pressures too low to permit their potency to be evident when given alone.

Alkanes↗
PubMed1993

Electrical stimulation as a substitute for the tail clamp in the determination of minimum alveolar concentration.

Circumstances may preclude the use of standard stimuli, namely tail clamp or surgical incision, to determine minimum alveolar concentration. In rats anesthesized with isoflurane, an alternative stimulus, electrical currents (10, 15, 20, or 40 V; biphasic pulses of 6.5 ms duration; 50 Hz), gave results comparable to those obtained with the tail clamp and the results did not change with repeated measurements if care was taken to avoid desensitization by exhaustion of a particular set of electrodes. The 40 V stimulation gave slightly higher values (4%; P < 0.006) than tail clamp, but the difference was too small to be of experimental significance. More importantly, the higher voltages produced desensitization after fewer attempts at stimulation. In addition to these results with isoflurane, we found that 15 V stimulation and tail clamp produced comparable minimum alveolar concentration values for halothane and for desflurane.

Anesthesia, Inhalation↗
PubMed1992

Tumour cell proliferation is abolished by inhibitors of Na+/H+ and HCO3-/Cl- exchange.

Cell membrane-associated ion transporters, Na+/H+ exchanger and Na(+)-dependent HCO3-/Cl- antiport, were shown to be important in the regulation of acidic intracellular pH in different cell types. This study investigated the role of the ion exchangers and their inhibitors in the serum-induced proliferation of two murine tumour cell lines, P815 and L929. The presence of Na+/H+ exchanger [inhibited by amiloride and 5-(N-ethyl-N-isopropyl)amiloride (EIPA)] and Na(+)-dependent HCO3-/Cl- antiport [inhibited by 4,4'-diisothiocyanostilbene-2,2-disulphonic acid (DIDS)] was shown on the tumour cell line tested. EIPA suppressed tumour cell proliferation more strongly than amiloride, and its effect was further increased after intracellular acidification by nigericin. DIDS slightly inhibited proliferation of L929 cell line and did not influence proliferation of P815 cells. However, in nigericin acidified cells DIDS had a dose dependent antiproliferative effect. Furthermore, DIDS significantly increased antiproliferative effects of amiloride and EIPA, suggesting the activity of Na(+)-dependent HCO3-/Cl- antiport in tumour cell proliferation. These results demonstrate the importance of Na(+)-dependent HCO3-/Cl- exchange in addition to Na+/H+ antiport, in tumour cell proliferation and indicate the possibility that ion exchange inhibitors could act as antitumour reagents.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Cerebral uptake and elimination of desflurane, isoflurane, and halothane from rabbit brain: an in vivo NMR study.

The authors used in vivo 19F nuclear magnetic resonance spectroscopy to determine rates of cerebral uptake and elimination of desflurane, isoflurane, and halothane in rabbits. After anesthetizing animals by intramuscular and intravenous injection of methohexital and inhalation of 70% nitrous oxide, intravenous and intraarterial catheters were inserted and a tracheostomy and craniotomy performed. Ventilation was controlled to maintain arterial carbon dioxide tension (PaCO2) from between 35 and 45 mmHg. A 2-2.5-cm diameter circle of dura was exposed, over which a 0.9 x 1.0-cm elliptical surface coil was placed. Cerebral anesthetic concentrations (CC) were estimated from spectra acquired on a 4.7-Tesla spectrometer. Alveolar uptake and elimination also were assessed, using inspired (FI) and end-tidal (denoted FA0 at the end of administration) concentrations measured by gas chromatography. After baseline spectra were obtained, volatile agents were administered for 30 min, followed by a 120-min period of elimination. Our findings demonstrate that cerebral uptake and elimination correlate with solubility: they are most rapid for desflurane, next most rapid for isoflurane, and least rapid for halothane. During administration, cerebral uptake of desflurane (CC/FI = 0.690 +/- 0.049 at 9 min) was approximately 1.7 times faster than isoflurane (CC/FI = 0.691 +/- 0.020 at 15 min) and 3 times faster than halothane (CC/FI = 0.662 +/- 0.040 at 27 min). Similarly, elimination rates for desflurane (CC/FA0 = 0.238 +/- 0.015 at 9 min) were 1.7 times faster than isoflurane (CC/FA0 = 0.236 +/- 0.017 at 15 min) and three times faster than halothane (CC/FA0 = 0.212 +/- 0.033 at 27 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

No EEG evidence of acute tolerance to desflurane in swine.

Desflurane is a potent inhaled anesthetic associated with a dose-dependent depression of cortical electrical activity. Recently, it has been suggested that the burst suppression pattern seen in dogs given moderately high doses (2.0 MAC) of desflurane may spontaneously subside. This observation suggests the development of acute tolerance to at least some of the anesthetic effects of this drug. No other volatile anesthetic has been found to produce acute tolerance. We attempted to replicate these findings in domestic swine. Five juvenile swine (25-30 kg) were anesthetized with desflurane in oxygen and during normocapnia were exposed to two doses of desflurane sufficient to induce burst suppression (1.5 and 1.7 MAC) for 35 min at each dose, with a period of EEG recovery (0.6 MAC) before, between (in 3 of 5 animals), and after the high doses. Frontoparietal EEG was continuously recorded and the burst suppression ratio continuously calculated. Suppression was more complete at 1.7 MAC than at 1.5 MAC (98.24 +/- 1.75 vs. 90.80 +/- 3.05%, respectively, mean +/- standard deviation). The degree of burst suppression activity did not change over time at either 1.5 (P greater than 0.33) or 1.7 MAC desflurane (P greater than 0.41). There was no EEG evidence of tolerance to desflurane anesthesia in swine.

Anesthesia, Inhalation↗