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S Patel

Publications and source records attributed to S Patel.

At least 127 records · Page 7Linked to original sources
PubMed2001

The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain.

We have examined the effects of cannabinoid agonists on hyperalgesia in a model of neuropathic pain in the rat and investigated the possible sites of action. The antihyperalgesic activity of the cannabinoids was compared with their ability to elicit behavioural effects characteristic of central cannabinoid activity. WIN55,212-2 (0.3-10 mg kg(-1)), CP-55,940 (0.03-1 mg kg(-1)) and HU-210 (0.001-0.03 mg kg(-1)) were all active in a 'tetrad' of tests consisting of tail-flick, catalepsy, rotarod and hypothermia following subcutaneous administration, with a rank order of potency in each of HU-210 > CP-55,940 > WIN55,212-2. The effects of WIN55,212-2 in each assay were blocked by the Cannabinoid1 (CB1) antagonist SR141716A. In the partial sciatic ligation model of neuropathic pain WIN55,212-2, CP-55,940 and HU-210 produced complete reversal of mechanical hyperalgesia within 3 h of subcutaneous administration with D50 values of 0.52, 0.08 and 0.005 mg kg(-1), respectively. In this model WIN55,212-2 was also effective against thermal hyperalgesia and mechanical allodynia. WIN55,212-2 produced pronounced reversal of mechanical hyperalgesia following intrathecal administration that was blocked by the CB1 antagonist SR141716A. Following intraplantar administration into the ipsilateral hindpaw, WIN55,212-2 produced up to 70% reversal of mechanical hyperalgesia, although activity was also observed at high doses following injection into the contralateral paw. The antihyperalgesic effect of WIN55,212-2 injected into the ipsilateral paw was blocked by subcutaneously administered SR141716A, but was not affected by intrathecally administered SR141716A. These data show that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via an action in both the CNS and in the periphery.

Analgesics↗
PubMed2001

Coordination of Ca2+ signalling by NAADP.

Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes intracellular Ca2+ stores in several cell types. Ample evidence suggests that NAADP activates intracellular Ca2+ channels distinct from those that are sensitive to inositol trisphosphate and ryanodine/cyclic ADP-ribose. Recent studies in intact cells have demonstrated functional coupling ('channel chatter') between Ca2+ release pathways mediated by NAADP, inositol trisphosphate and cyclic ADP-ribose. Thus, NAADP is probably an important determinant in shaping cytosolic Ca2+ signals.

Calcium Signaling↗
PubMed2001

An in vivo binding assay to determine central alpha(1)-adrenoceptor occupancy using [(3)H]prazosin.

An alpha(1) adrenoceptor (alpha(1)-AdR) assay using [(3)H]prazosin binding in mouse brain is described which allows in vivo determination of central alpha(1)-AdR occupancy for ligands with alpha(1)-AdR affinity. Binding of [3H]prazosin in rat and mouse brain membranes in vitro was used to characterise the pharmacological profile of alpha(1)-AdRs in order to determine any potential species variations. Saturation and displacement studies yielded comparable affinity and pharmacological profile for [(3)H]prazosin binding in mouse and rat brain homogenates. These studies confirmed the absence of species variation for ligands in central alpha(1)-AdR pharmacology which is in good agreement with previous studies in rat brain. Subsequently, in vivo binding of [(3)H]prazosin in mouse whole brain was used to measure the occupancy of a number of AdR ligands. Timecourse studies revealed that a [3H]prazosin (5 mu Ci/mouse) pretreatment time of at least 20 min following intravenous (i.v.) administration was required for optimal specific binding. Ligands were administered systemically 40 min prior to i.v. administration of radiolabel. The alpha(1)-adrenoceptor ligands prazosin (ED(50)=0.15 mg/kg i.p.), benoxathian (0.52 mg/kg i.p.) and phentolamine (51 mg/kg i.p.) were all able to block in vivo [(3)H]prazosin binding from mouse brain. In addition, receptor occupancy values for a number of compounds including haloperidol (ED(50)=0.83 mg/kg s.c.), clozapine (2.2 mg/kg s.c.) and MDL-100907 [R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol], (10 mg/kg s.c.)], which possess high to moderate affinity at alpha(1)-adrenoceptors, were also determined. These results suggest that in the mouse, [(3)H]prazosin binding can be used to measure in vivo receptor occupancy of ligands with affinity at central alpha(1)-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed2001

Regulation of organelle membrane fusion by Pkc1p.

Membrane fusion relies on complex protein machineries, which act in sequence to catalyze the fusion of bilayers. The fusion of endoplasmic reticulum membranes requires the t-SNARE Ufe1p, and the AAA ATPase p97/Cdc48p. While the mechanisms of membrane fusion events have begun to emerge, little is known about how this fusion process is regulated. We provide first evidence that endoplasmic reticulum membrane fusion in yeast is regulated by the action of protein kinase C. Specifically, Pkc1p kinase activity is needed to protect the fusion machinery from ubiquitin-mediated degradation.

Adenosine Triphosphatases↗
PubMed2001

Oral antioxidant therapy for marginal dry eye.

OBJECTIVE: To assess the efficacy of an orally administered antioxidant dietary supplement for managing marginal dry eye. DESIGN: A prospective, randomised, placebo controlled trial with cross-over. SETTING: Eye Clinic, Department of Vision Sciences, Glasgow Caledonian University. SUBJECTS: Forty marginal dry eye sufferers composed of 30 females and 10 males (median age 53 y; range 38-69 y). INTERVENTIONS: Baseline assessments were made of tear volume sufficiency (thread test), tear quality (stability), ocular surface status (conjunctival impression cytology) and dry eye symptoms (questionnaire). Each subject was administered courses of active treatment, placebo and no treatment, in random order for 1 month each and results compared to baseline. RESULTS: Tear stability and ocular surface status were significantly improved following active treatment (P<0.05). No changes from baseline were detected following administration of placebo and no treatment (P>0.05). Absolute increase in tear stability correlated with absolute change in goblet cell population density. Tear volume was not improved following any treatment period and dry eye symptom responses were subject to placebo effect. CONCLUSIONS: Oral antioxidants improved both tear stability and conjunctival health, although it is not yet understood whether increased ocular surface health mediates increased tear stability or vice versa. SPONSORS: This study was supported by a PhD scholarship funded by the Department of Vision Sciences, Glasgow Caledonian University, Scotland. Antioxidant supplements and placebos were kindly donated by Vitabiotics.

Administration, Oral↗
PubMed2001

Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells.

Preclinical models for the identification of prostate cancer chemoprevention agents are lacking. Based upon the notion that clinically useful chemoprevention agents should exhibit selective activity against early stage disease, studies were undertaken to assess whether chemoprevention agents selectively inhibited the growth of early stage prostate cancer, as compared to late stage cancer. First, a series of cell and molecular studies were performed, which, when taken together, validated the use of a panel of prostate cell lines as a model of the different stages of carcinogenesis. Next, therapeutic responsiveness to ten different cytotoxic or chemoprevention agents was evaluated. Chemoprevention agents exhibited selective activity against normal and early transformed prostate tissue, whereas cytotoxic agents were non-specific. Selective activity against early versus advanced prostate cancer cells is identified as a potential screening method for chemoprevention agents.Prostate Cancer and Prostatic Diseases (2001) 4, 81-91

Journal Article↗
PubMed2001

Epidemiological study of oesophageal and gastric cancer in south-east England.

BACKGROUND: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. METHODS: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960-1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. RESULTS: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change + 0.05 for men, + 0.009 for women). For the gastric cardia, the incidence in males increased (average annual change + 0.025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change + 0.07 for men, + 0.009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. CONCLUSION: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes.

Adolescent↗
PubMed2001

TBI or not TBI: that is the question. Is it better to measure toe pressure than ankle pressure in diabetic patients?

AIMS: Measurement of ankle blood pressure is a simple method of assessing lower limb arterial blood supply. However, its use in diabetes has been questioned due to the presence of medial artery calcification. Measurement of toe blood pressure has been advocated as an alternative but it is technically more difficult. The aim of this study was to obtain information to guide clinicians as to when pressure measurements should be taken at the toe. METHODS: Ankle brachial index (ABI) and toe brachial index (TBI) were measured by Doppler ultrasound, or photoplethysmography on 174 subjects with diabetes and 53 control subjects. The Bland and Altman method, and the Cohen's method of measuring agreement between two tests were used to compare ABI with TBI. RESULTS: The mean differences between ABI and TBI in control and diabetic subjects are 0.40 +/- 0.13 and 0.37 +/- 0.15, respectively. Nearly all diabetic patients with an ABI < 1.3 have an ABI-TBI gradient falling within the normal range established from the non-diabetic cohort. In contrast, the majority of diabetic subjects with an ABI > or = 1.3 have ABI-TBI differences outside this range. When patients are categorized according to ABI and TBI, there is also good agreement between the tests when ABI is low or normal (84% and 78% agreement, respectively), but not when ABI is elevated. CONCLUSION: In the majority of patients with diabetes, assessment of TBI conveys no advantage over ABI in determining perfusion pressure of the lower limbs. Only in those patients with overt calcification, which gives an ABI > or = 1.3, are toe pressure measurements superior. This guideline should simplify assessment and treatment of diabetic patients with disease of the lower limbs. Diabet. Med. 18, 528-532 (2001)

Adult↗
PubMed2001

The minimum stimulus energy required to produce a cooling sensation in the human cornea.

PURPOSE: To estimate the minimum stimulus energy required to stimulate the corneal nerves, using a thermally cooling stimulus. METHODS: The localised temperature change produced in the pre-corneal tear film by the air-pulse stimulus of the Non-Contact Corneal Aesthesiometer (NCCA) was analysed using a thermal imaging camera. Assuming that the cornea behaves as a near perfect black-body, the threshold for energy loss was calculated by combining Stefan-Boltzmann's law and Kirchoff's law for imperfections in black-body radiation, taking into account the likely thermal conductivity of the human cornea. RESULTS: The average normal subject has a threshold for detecting a cooling effect when the local corneal tear film surface temperature drops from a mean of 33.2-32.9 degrees C (i.e. 0.3 degrees C), over a 1 mm diameter circular area (0.785 mm2), and a stimulus time duration of 0.9 s. This gives rise to a sensation threshold for perceiving a loss of heat energy of 7.0 ergs, or 7.0 x 10(-7) joules. CONCLUSION: The cornea possesses stimulus specific receptors, which have an exquisite sensitivity to a rapid, thermally cooling stimulus.

Cold Temperature↗
PubMed2001

Allelic loss analysis by capillary electrophoresis: an accurate, automated method for detection of deletions in solid tumors.

In this report, we describe a fast and accurate capillary electrophoresis, PCR-based method for detecting loss of allelic heterozygosity in solid tumor samples. This automated method requires small sample sizes, and data can be obtained in less than 15 min. The method is particularly powerful for uncovering deletions in tumor sample preparations containing significant normal tissue contamination.

Chromosomes, Human, Pair 7↗
PubMed2001

Relationship between age and plasma esterases.

INTRODUCTION: the older population is the most medicated. Despite high drug usage, older people are generally excluded from the research underpinning new drug development. This means that drugs are prescribed to older people with very little understanding of how they are likely to metabolize them. More research is needed to investigate the possible effects of ageing on the biotransformation of drugs. We therefore undertook a cross-sectional study examining the effect of age on the activities of benzoylcholinesterase, butyrylcholinesterase, acetylcholinesterase and aspirin esterase. METHODS: we measured the activities of benzoylcholinesterase and butyrylcholinesterase in 70 healthy volunteers aged 18-85 years. We measured the activities of acetylcholinesterase and aspirin esterase in 43 healthy volunteers aged 18-85 years. We determined plasma activities of benzoylcholinesterase, butyrylcholinesterase, acetylcholinesterase and aspirin esterase spectrophotometrically. RESULTS: we found no correlation between the activities of any of the enzymes measured and advancing age. CONCLUSION: age per se is not associated with reductions in the activities of esterase enzymes.

Acetylcholinesterase↗
PubMed2001

Interactions between the inositol 1,4,5-trisphosphate and cyclic AMP signaling pathways regulate larval molting in Drosophila.

Larval molting in Drosophila, as in other insects, is initiated by the coordinated release of the steroid hormone ecdysone, in response to neural signals, at precise stages during development. In this study we have analyzed, using genetic and molecular methods, the roles played by two major signaling pathways in the regulation of larval molting in Drosophila. Previous studies have shown that mutants for the inositol 1,4,5-trisphosphate receptor gene (itpr) are larval lethals. In addition they exhibit delays in molting that can be rescued by exogenous feeding of 20-hydroxyecdysone. Here we show that mutants for adenylate cyclase (rut) synergize, during larval molting, with itpr mutant alleles, indicating that both cAMP and InsP(3) signaling pathways function in this process. The two pathways act in parallel to affect molting, as judged by phenotypes obtained through expression of dominant negative and dominant active forms of protein kinase A (PKA) in tissues that normally express the InsP(3) receptor. Furthermore, our studies predict the existence of feedback inhibition through protein kinase A on the InsP(3) receptor by increased levels of 20-hydroxyecdysone.

Adenylyl Cyclases↗
PubMed2001

The effect of long-term, daily contact lens wear on corneal sensitivity.

PURPOSE: To assess the effect of long-term, daily-wear soft contact lenses and rigid gas permeable (RGP) contact lenses on corneal sensitivity using a noninvasive, air-pulse stimulus. METHODS: The central and peripheral (temporal, medial, inferior) corneal sensation thresholds of 40 non-lens wearers, 40 soft lens wearers, and 40 RGP lens wearers were assessed using the Non-Contact Corneal Aesthesiometer (NCCA). The individuals who wore contact lenses were grouped according to the number of years of lens wear (10 years or less, 11-20 years, and 21 years or more). RESULTS: Although a significant reduction in corneal sensitivity was found between the contact lens wearers and non-lens wearers (p = 0.000), no difference was found between the two lens-type subgroups (p = 0.939). This pattern of significance was repeated at each of the peripheral test locations. No relationship between corneal sensitivity and years of lens wear was found centrally (r2 = 0.004) or at any of the peripheral test locations. No significant difference was found between the central corneal sensation thresholds for the different subgroups of lens wear duration (p = 0.469) or for any of the peripheral test locations. CONCLUSIONS: Both soft and RGP lens wear produce a similar type of corneal sensitivity loss, although the mechanism for this loss is different for the two lens types. The extent of sensitivity loss is not related to the duration of lens wear and appears to plateau after the first few months of wear. No topographical variation in sensitivity loss was found with lens type or with the duration of lens wear.

Adult↗
PubMed2001

Intracranial surgery: to shave or not to shave?

OBJECTIVE: In an effort to improve patient confidentiality as well as cosmesis, the authors have stopped shaving for all intracranial procedures. The objective was to determine whether this lack of shaving increased the postoperative infection rate. DESIGN: A retrospective study was performed comparing all intracranial surgical procedures performed in the last 2(1/2) years, when hair was not shaved, with the infection rate in patients who did have their hair shaved in the preceding 3(1/2) years. SETTING: An academic tertiary care referral center. PATIENTS: Every patient (children and adults) who underwent an intracranial procedure by the skull base surgery team was included. Similar patient demographics were used for the hair-shaved group. INTERVENTION(S): Intracranial procedures consisted of acoustic tumor removal, vestibular nerve sections, skull base surgery procedures, vascular decompressions, and craniotomies for benign and malignant tumors. MAIN OUTCOME MEASURES: The most essential criterion was to determine whether postoperative wound infection developed in a patient. This was documented as either minor (stitch abscess or wound dehiscence), moderate (wound breakdown requiring inpatient or outpatient therapy, such as oral or intravenous antibiotics), or severe (significant wound breakdown that required hospitalization, with surgical debridement and antibiotics). RESULTS: In all, 150 patients were not shaved for their intracranial procedures; postoperative wound infections developed in 11 (7%). The infections were minor (6), moderate (5), and severe (0). By comparison, 100 patients undergoing intracranial procedures had their hair shaved. In this group, the number of infections noted was 6 (6%). Their categorization into mild, moderate, and severe was 4, 2, and 0, respectively. Statistical analysis did not reveal any significant difference between the two infection rates. CONCLUSIONS: The rate of postoperative wound infection was statistically no greater when the hair was shaved than when it was not. Thus, for patient confidentiality as well as patient esteem, we recommend not shaving hair for intracranial procedures.

Adult↗