Biomedical subjects

T Bhatti

Publications and source records attributed to T Bhatti.

At least 19 recordsLinked to original sources

PubMed2003

Vanilloid receptor activation by 2- and 10-microm particles induces responses leading to apoptosis in human airway epithelial cells.

Exposure to airborne particulate matter (PM) is associated with increased mortality and morbidity. It has been previously shown that PMs and synthetic particles (PC10 and PC2) that have similar characteristics to PMs induced depolarizing currents and increases in intracellular calcium ([Ca2+]i) in capsaicin- and acid-sensitive sensory neurons and in TRPV1-expressing HEK 293 cells. To determine whether such mechanisms also underlie PM-induced toxicity in epithelial cells lining the human airways, we tested the responses of PCs on BEAS-2B (immortalized human bronchial epithelial cells), NHBE (normal human bronchial/tracheal epithelial cells), and SAEC (normal human small airway epithelial cells from the distal airways). RT-PCR revealed that all these cell types expressed TRPV1 (VR1), ASIC1a, and ASIC3 subunits of proton-gated ion channels. Calcium imaging studies revealed that in all three cell types approximately 30% were activated by both capsaicin and acid. In these cells, PCs induced an increase in [Ca2+]i that was inhibited by capsazepine, a TRPV1 antagonist, and/or by amiloride, an ASIC antagonist. The capsazepine-sensitive contribution to PC-induced increases in [Ca2+]i was approximately 70%. Measurements of apoptosis revealed that exposure to PCs induced a time-dependent increase in the number of apoptotic cells. After incubation for 24 (PC10) or 48 h (PC2) approximately 60% of these cells were apoptotic. Pretreatment with capsazepine as well as removal of external calcium completely (approximately 100%) prevented PC-induced apoptosis. These data suggest that pharmacological inhibition of calcium-permeable vanilloid receptors could be used to prevent some of the pathological actions of PMs.

Air Pollutants↗

PubMed2000

Clinical and physiological consequences of rapid tryptophan depletion.

We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in remitted patients with a history of depression but not in patients treated with antidepressants which promote catecholaminergic rather than serotonergic neurotransmission (such as tricyclic antidepressants or buproprion). However, RTD has inconsistent effects in terms of full clinical relapse in depressed patients. Pooling the data from all published reports, patients who are either unmedicated and/or fully remitted are much less likely to experience relapse (7 of 61, or approximately 9%) than patients who are recently medicated and partially remitted (63 of 133, or approximately 47%; although, the numbers here may reflect patient overlap between reports). Recently remitted patients who have been treated with non-pharmacological therapies such as total sleep deprivation, electroconvulsive therapy, or bright light therapy also do not commonly show full clinical relapse with RTD. We briefly review RTD effects in other psychiatric disorders, many of which are treated with SSRIs. There is accumulating evidence to suggest that RTD affects central serotonergic neurotransmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce symptoms in unmedicated symptomatic or asymptomatic patients.

Antidepressive Agents↗

PubMed1998

Sleep electroencephalographic response to muscarinic and serotonin1A receptor probes in patients with major depression and in normal controls.

BACKGROUND: To test the hypothesis that depression is associated with an increased ratio of cholinergic to serotonergic neurotransmission, we compared the effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5-HT)1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy subjects. We hypothesized, adopting the reciprocal interaction model, that the effects on REM sleep of these probes within the same individuals are negatively correlated and unmask neurobiological changes in depression. METHODS: Polysomnographic recordings were obtained in 12 unmedicated patients with a current major depression and 12 normal controls. They received placebo, pilocarpine 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after premedication with the peripheral anticholinergic probanthine 30 mg, double blind, counterbalanced) on three occasions. RESULTS: Pilocarpine shortened and ipsapirone prolonged REM latency equally in both groups. These effects were not correlated. Pilocarpine decreased slow-wave sleep and EEG delta power during the first nonREM episode more in controls than in patients, and enhanced EEG sigma power equally in both groups. Ipsapirone had no significant effects on EEG power. CONCLUSION: These data do not support the postulate of muscarinic receptor up-regulation and 5-HT1A receptor down-regulation in depression. The significance of blunted delta power suppression in patients following pilocarpine warrants further investigations.

Adult↗

PubMed1998

Effects of a tryptophan-free amino acid drink challenge on normal human sleep electroencephalogram and mood.

BACKGROUND: Serotonin has been implicated in the regulation of sleep and mood. In animals a tryptophan-free amino acid drink (TFD) challenge has been found to reduce brain serotonin. We hypothesized this TFD would produce alterations in electroencephalographic (EEG) sleep commonly associated with depression, i.e. an enhancement of rapid eye movement (REM) sleep, and adversely affect mood ratings in humans. METHODS: We investigated the effects of a TFD challenge in 11 healthy male subjects on EEG sleep and mood (assessed by Profile of Mood States). All subjects received on separate occasions an experimental drink containing approximately 100 g of an amino acid mixture (100% TFD) and a control drink containing one fourth strength (25% TFD) of the experimental drink 5 hours prior to sleep (6:00 PM). RESULTS: Both drinks significantly decreased plasma tryptophan levels 5 hours postchallenge (11:00 PM). Both drinks significantly decreased REM latency, and the 25% TFD also increased REM time and REM% compared to baseline. No significant changes were found in subjective ratings of depression; however, subjects reported confusion and tension and a decrease in elation, vigor, and friendliness compared with baseline. CONCLUSIONS: These TFD findings further support the involvement of serotonin deficiency in EEG sleep findings commonly seen in depression.

Adult↗

PubMed1998

Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with remitted depression on serotonin reuptake inhibitors.

BACKGROUND: In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree. CONCLUSIONS: Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.

Amino Acids↗

PubMed1996

The 5-HT1A agonist ipsapirone enhances EEG slow wave activity in human sleep and produces a power spectrum similar to 5-HT2 blockade.

The REM sleep-suppressing effect of postsynaptic 5-HT1A stimulation has been well established. Here we investigate the effects of the 5-HT1A agonist ipsapirone (10 and 20 mg) on sleep EEG power spectra during non-REM sleep in nine healthy humans. At the lower dose, slow wave activity (SWA; EEG power in the delta (1-4.5 Hz) range) was significantly enhanced. At the higher dose, where side-effects occurred, the enhancement in SWA was not significant. The spectral profile was characterized by a bimodal increase of power in the lower delta and in the theta (5-8 Hz) frequencies, and by troughs at 4 Hz and at 11 Hz, a pattern compellingly similar to that reported for a 5-HT2 antagonist (seganserin). We propose that the spectral data following the lower ipsapirone dose reflect a net decrease of neuronal activity at 5-HT2 receptors, mediated through stimulation of somatodendritic autoreceptors in the raphe nuclei (presynaptic) and/or through stimulation of postsynaptic 5-HT1A receptors colocalized with 5-HT2 receptors. The spectral non-REM sleep EEG profile might be used to investigate central 5-HT function in humans.

Adult↗

PubMed1995

Specific inhibition of the contraction of the rat aorta by estradiol 17 beta.

Short-term exposure to estradiol 17 beta is known to inhibit the contraction of vascular smooth muscle preparations that is thought to be mediated by a [Ca++]-dependent mechanism. The purpose of this investigation was to examine the effect of prolonged exposure of vascular preparations to estradiol 17 beta to provide significant time for protein synthesis. We find that treatment of rat aortic rings with estradiol 17 beta (0.37-37 microM) for 15 to 180 min and subsequent removal of the estrogen by washing, attenuated the vasoconstrictor responses to phenylephrine and potassium chloride in a time-dependent manner. The maximum inhibitory effect took 120 min to develop. The inhibitory effect was endothelium independent and not blocked by the cyclooxygenase inhibitor, indomethacin, or by the endothelium derived relaxing factor inhibitor, Nw-nitro-L-arginine methyl ester. This effect was highly stereo-specific in that the 17 alpha isomer was significantly less potent than the 17 beta isomer of estradiol. Further, compared to other steroids, estradiol 17 beta was the most potent. The inhibitory effect of estradiol was blocked completely by pretreatment with the protein synthesis inhibitors, cycloheximide and puromycin, but not by actinomycin D. Electron microscopy showed an increase in ribosomal expression at the rough endoplasmic reticulum after incubation of the rat aorta with estradiol for 120 min. This indicates increased protein synthesis after exposure to estradiol 17 beta. We speculate that the time dependent inhibitory effect of estradiol 17 beta on vascular smooth muscle is related to protein synthesis at the translational level.

Animals↗

PubMed1993

Protection by oestradiol against the development of cardiovascular changes associated with monocrotaline pulmonary hypertension in rats.

1. We studied the effects of oestradiol 17 beta on the development of pulmonary vascular changes and right ventricular (RV) hypertrophy in response to monocrotaline in male Sprague-Dawley rats. 2. Rats were treated with either placebo or oestradiol 17 beta (10 mg) in the form of slow release pellets implanted subcutaneously 48 h before monocrotaline administration. Rats were injected with either saline or a single dose of monocrotaline (60 mg kg-1, i.m.). Pulmonary vascular changes and RV hypertrophy were studied at 4 weeks following monocrotaline administration. 3. Monocrotaline induced a significant increase in the ratio of right ventricle (RV) to left ventricle-plus-septum (LV + S) weights. Monocrotaline-treated rats also showed significant myointimal proliferation in small pulmonary arteries, decrease of arterial numbers and increase in the number of abnormal alveolar macrophages. 4. Oestradiol 17 beta attenuated myointimal hyperplasia in pulmonary vessels, decreased the RV/(LV + S) ratio in monocrotaline-treated rats. Oestradiol 17 beta had no significant effect on control animals. 5. Oestradiol treatment prevented the increase in lung wet to dry weight ratio, observed 7 days post monocrotaline administration. 6. These results suggest that oestradiol 17 beta protects against the pulmonary vascular remodelling and RV hypertrophy associated with monocrotaline-induced pulmonary hypertension in the rat. Oestradiol also protects against microvascular leak observed in the early days of lesion.

Animals↗

PubMed1993

The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit.

BACKGROUND: Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied. METHODS AND RESULTS: Three rabbits received 125I-angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three angiopeptin groups receiving 1, 10, or 100 micrograms/mL of angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the angiopeptin groups compared with the control group. However, in the lower abdominal aorta, where balloon injury without local delivery was performed, there was a significant reduction of myointimal hyperplasia in the highest-concentration angiopeptin group (P < .001 versus the control group). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the angiopeptin-treated animals, endothelial cells were present at both locations. CONCLUSIONS: Angiopeptin can be delivered intramurally via the Wolinsky porous balloon and reduces myointimal hyperplasia only in the area distal to the local drug delivery site (downstream effect), possibly by healing the injured endothelium, by transport via the vasa vasora, and/or by systemic effect.

Amino Acid Sequence↗

PubMed1992

Electrophoretic analysis of snake venoms.

Electrophoretic analyses were conducted on snake venoms from 21 species representing Elapidae, Crotalidae and Viperidae. Denatured and native venoms were analyzed by polyacrylamide gel electrophoretic (PAGE) methods with sodium dodecyl sulfate (SDS) and without SDS. Both SDS-PAGE and PAGE profiles of venoms from different snake species indicate that some proteins and polypeptide components of these venoms have common electrophoretic characteristics suggesting a genetic relationship. Conversely, the electropherograms also showed the characteristic protein and polypeptide profiles that could differentiate one snake species from another. Therefore, both SDS-PAGE and PAGE profiles suggest that proteins and polypeptides with similar characteristics abound among subspecies or related species, although each venom has a unique profile that differentiates one species from the other.

Animals↗

PubMed1990

Histopathological changes in gastrocnemius muscles of rabbits injected with HI-6 in saline.

The gastrocnemius muscles of rabbits were injected with HI-6 in saline. Macroscopic and histopathological examinations of injection sites and regional lymph nodes revealed that HI-6 in saline produced muscle necrosis. Macroscopic examinations of muscles injected with a low dose of HI-6 (50 mg/kg) showed no lesions on Day 7. However, histopathological examinations disclosed lesions on some animals but with evidence of healing processes by Day 7; lesions disappeared by Day 14. Further macroscopic and histopathological examinations revealed that lesions associated with the high dose (200 mg/kg) were still prominent on Day 14 but with evidence of healing. Similar lesions seen in muscles injected with saline were significantly less persistent than those associated with HI-6.

Animals↗

PubMed1971