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Biomedical subjects

M S Nash

Publications and source records attributed to M S Nash.

At least 19 recordsLinked to original sources
PubMed2005

Linking land cover and water quality in New York City's water supply watersheds.

The Catskill/Delaware reservoirs supply 90% of New York City's drinking water. The City has implemented a series of watershed protection measures, including land acquisition, aimed at preserving water quality in the Catskill/Delaware watersheds. The objective of this study was to examine how relationships between landscape and surface water measurements change between years. Thirty-two drainage areas delineated from surface water sample points (total nitrogen, total phosphorus, and fecal coliform bacteria concentrations) were used in step-wise regression analyses to test landscape and surface-water quality relationships. Two measurements of land use, percent agriculture and percent urban development, were positively related to water quality and consistently present in all regression models. Together these two land uses explained 25 to 75% of the regression model variation. However, the contribution of agriculture to water quality condition showed a decreasing trend with time as overall agricultural land cover decreased. Results from this study demonstrate that relationships between land cover and surface water concentrations of total nitrogen, total phosphorus, and fecal coliform bacteria counts over a large area can be evaluated using a relatively simple geographic information system method. Land managers may find this method useful for targeting resources in relation to a particular water quality concern, focusing best management efforts, and maximizing benefits to water quality with minimal costs.

Agriculture↗
PubMed2001

Single-cell imaging of graded Ins(1,4,5)P3 production following G-protein-coupled-receptor activation.

The pleckstrin homology domain of phospholipase Cdelta1 (PH(PLCdelta)) binds Ins(1,4,5)P(3) and PtdIns(4,5)P(2) specifically, and can be used to detect changes in Ins(1,4,5)P(3) in single cells. A fusion construct of PH(PLCdelta) and enhanced green fluorescent protein (EGFP-PH(PLCdelta)) associates with the plasma membrane due to its association with PtdIns(4,5)P(2). However, PH(PLCdelta) has greater affinity for Ins(1,4,5)P(3) than PtdIns(4,5)P(2), and translocates to the cytosol as Ins(1,4,5)P(3) levels rise. Prolonged activation of group I metabotropic glutamate receptor 1alpha expressed in Chinese-hamster ovary cells or endogenous M(3) muscarinic receptors in SH-SY5Y neuroblastoma cells gave an initial transient peak in translocation, followed by a sustained plateau phase. This closely followed changes in cell population Ins(1,4,5)P(3) mass, but not PtdIns(4,5)P(2) levels, which decreased monophasically, as determined by radioreceptor assay. Translocation thus provides a real-time method to follow increases in Ins(1,4,5)P(3). Graded changes in Ins(1,4,5)P(3) in Chinese-hamster ovary-lac-mGlu1alpha cells could be detected with increasing glutamate concentrations, and dual loading with fura 2 and EGFP-PH(PLCdelta) showed that changes in intracellular Ca(2+) concentration closely paralleled Ins(1,4,5)P(3) production. Moreover, Ins(1,4,5)P(3) accumulation and intracellular Ca(2+) mobilization within single cells is graded in nature and dependent on both agonist concentration and receptor density.

Animals↗
PubMed2001

Reassessment of the Ca2+ sensing property of a type I metabotropic glutamate receptor by simultaneous measurement of inositol 1,4,5-trisphosphate and Ca2+ in single cells.

Transient transfection of Chinese hamster ovary or baby hamster kidney cells expressing the Group I metabotropic glutamate receptor mGlu1alpha with green fluorescent protein-tagged pleckstrin homology domain of phospholipase Cdelta1 allows real-time detection of inositol 1,4,5-trisphosphate. Loading with Fura-2 enables simultaneous measurement of intracellular Ca(2+) within the same cell. Using this technique we have studied the extracellular calcium sensing property of the mGlu1alpha receptor. Quisqualate, in extracellular medium containing 1.3 mm Ca(2+), increased inositol 1,4,5-trisphosphate in all cells. This followed a typical peak and plateau pattern and was paralleled by concurrent increases in intracellular Ca(2+) concentration. Under nominally Ca(2+)-free conditions similar initial peaks in inositol 1,4,5-trisphosphate and Ca(2+) concentration occurred with little change in either agonist potency or efficacy. However, sustained inositol 1,4,5-trisphosphate production was substantially reduced and the plateau in Ca(2+) concentration absent. Depletion of intracellular Ca(2+) stores using thapsigargin abolished quisqualate-induced increases in intracellular Ca(2+) and markedly reduced inositol 1,4,5-trisphosphate production. These data suggest that the mGlu1alpha receptor is not a calcium-sensing receptor because the initial response to agonist is not sensitive to extracellular Ca(2+) concentration. However, prolonged activation of phospholipase C requires extracellular Ca(2+), while the initial burst of activity is highly dependent on Ca(2+) mobilization from intracellular stores.

Animals↗
PubMed2001

Enhanced inducible mGlu1alpha receptor expression in Chinese hamster ovary cells.

Inducible expression of the group-I metabotropic glutamate receptor (mGlu1alpha) in Chinese hamster ovary cells allows for the study of receptor density dependent effects. However, expression levels attainable with this system are lower than those reported for various brain regions and achieved by conventional (constitutive) transfection. Thus, direct comparison of mGlu1alpha receptor-mediated responses in this inducible expression system with those for receptors expressed heterologously or in vivo is compounded. We show here that inducible expression can be selectively augmented by butyrate pretreatment to levels approaching those reported for cerebral tissue. Enhanced mGlu1alpha receptor protein levels, agonist-induced inositol phosphate accumulation, as well as single-cell inositol 1,4,5-trisphosphate production and intracellular Ca(2+) mobilization occurred following co-induction with butyrate. In contrast, endogenous purinoceptor function was unaffected. Importantly, the ability to titrate receptor expression by varying isopropyl beta-thiogalactoside concentration was retained. Sodium butyrate thus offers a simple and convenient method to enhance inducible gene expression to levels found in vivo.

Animals↗
PubMed2001

Circuit resistance training improves the atherogenic lipid profiles of persons with chronic paraplegia.

BACKGROUND: People with chronic paraplegia frequently experience dyslipidemias characterized by depressed levels of high-density lipoprotein cholesterol (HDL-C) and elevated levels of low-density lipoprotein cholesterol (LDL-C). These abnormal lipid profiles and poor fitness levels increase their risk for cardiovascular disease. METHODS: To test the hypothesis that circuit resistance exercise training improves both upper-extremity fitness and the atherogenic lipid profile in persons with chronic paraplegia, a homogeneous cohort of 5 men with neurologically complete spinal cord injuries at T6 to L1 underwent 3 months of exercise training using uninterrupted resistance and endurance exercises of the upper extremities. Training was performed 3 times a week on alternating days. RESULTS: Results of graded arm exercise testing showed a 30.3% improvement in peak oxygen consumption (P < .01), a 33.5% increase in time to fatigue (P < .01) and a 30.4% increase in peak power output (P < .05). Pretraining total cholesterol levels (TC) were in the low-risk category and were nonsignificantly lowered following training. Similar nonsignificant reductions of plasma triglycerides averaging 12 mg/dL were attained. Conversely, a 25.9% lowering of LDL-C (P < .05) and 9.8% elevation of HDL-C (P < .05) were observed after training. These changes reduced the average LDL-C-to-HDL-C ratio by 1 unit (P < .05) and the TC-to-HDL-C ratio from 5.0 +/- 1.1 (mean +/- SD) to 3.9 +/- 0.7 (P < .05). CONCLUSIONS: This change reflects a cardiovascular risk reduction of almost 25%; the TC/HDL-C declined from the high-risk score of 5.0 to near the desired score of 3.5. These findings support the beneficial effects of circuit exercise resistance training on fitness and atherogenic lipid profiles in persons with chronic paraplegia.

Adult↗
PubMed2001

Modes, benefits, and risks of voluntary an delectrically induced exercise in persons with spinal cord injury.

BACKGROUND: Sedentary lifestyles and physical deconditioning are commonly reported among persons with spinal cord injury (SCI), although many forms of exercise have been shown to be beneficial. For individuals unable to perform voluntary exercise, involuntary exercise by electrically stimulated contractions has been used to train individual body segments, invoke cycling movements with or without arm propulsion, and stimulate ambulation. OBJECTIVE: To evaluate the benefits and risks associated with various modes of exercise in persons with SCI. METHODS: Literature review. FINDINGS: Electrical stimulation of local muscle sites increases muscle mass and circulation and favorably alters muscle fiber composition. Electrically stimulated cycling has been observed to improve fitness, lower-extremity circulation, and circulatory response to ischemia and to reverse cardiac muscle atrophy in persons with tetraplegia. Electrically stimulated ambulation improves upper-extremity endurance, lower-extremity circulation, and perception of body image. Studies of arm and wheelchair ergometry show increased arm endurance and decreased cardiovascular risks associated with hyperlipidemia, while resistance training of the upper extremities improves strength and endurance. Because autonomic hyperreflexia, orthostatic intolerance, thermal dysregulation, and fracture are associated with exercise in SCI, risk reduction strategies and prompt intervention are required. CONCLUSIONS: Well-designed programs of exercise are beneficial for persons with tetraplegia and paraplegia. Risks and benefits vary with level of injury. Programs need to address prevention of and intervention for potential adverse effects associated with exercise in individuals with spinal cord dysfunction.

Electric Stimulation Therapy↗
PubMed2001

Circuit training provides cardiorespiratory and strength benefits in persons with paraplegia.

PURPOSE: This study tested the safety and the effects of circuit resistance training (CRT) on peak upper extremity cardiorespiratory endurance and muscle strength in chronic survivors of paraplegia due to spinal cord injury. METHODS: Ten men with chronic neurologically complete paraplegia at the T5-L1 levels participated in the study. Subjects completed 12 wk of CRT, using a series of alternating isoinertial resistance exercises on a multi-station gym and high-speed, low-resistance arm ergometry. Peak arm ergometry tests, upper extremity isoinertial strength testing, and testing of upper extremity isokinetic strength were all performed before and after training. RESULTS: None of the subjects suffered injury from exercise training. Significant increases were observed in peak oxygen consumption (29.7%, P < 0.01), time to fatigue (P < 0.01), and peak power output during arm testing (P < 0.05). Significant increases in isoinertial strength for the training maneuvers ranged from 11.9% to 30% (Ps < 0.01). Significant increases in isokinetic strength were experienced for shoulder joint internal rotation, extension, abduction, adduction, and horizontal adduction (Ps < 0.05). CONCLUSION: Chronic survivors of paraplegia safely improve their upper extremity cardiorespiratory endurance and muscle strength when undergoing a short-term circuit resistance training program. Gains in fitness and strength exceeded those usually reported after either arm endurance exercise conditioning or strength training in this subject population.

Adult↗
PubMed2000

Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx.

The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified.

Aminopyridines↗
PubMed2000

5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies.

Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Known and plausible modulators of depressed immune functions following spinal cord injuries.

Recent evidence suggests that depression of immune function occurs early after spinal cord injury (SCI) and is maintained thereafter. Deviations from immune function observed in healthy persons with intact neuraxes include natural killer cell number and cytotoxicity, T cell function and activation, macrophage phagocytosis, levels of interleukins (IL)-2 and -6, the soluble IL-2R receptor, and intracellular adhesion molecules. While a single etiology explaining these abnormalities has not been identified, decentralization of the autonomic nervous system is the most likely cause. Otherwise, many persons with SCI, who sustain episodic autonomic overstimulation, are among the most physically deconditioned of all humans, and often select a diet rich in fat and low in protein. All of these are associated with suppressed immune function in persons without SCI. Those with SCI may also be (over)exposed to drugs and medications that suppress immune function, including methylprednisolone administered immediately after traumatic injury. No evidence suggests that the immune profiles of persons with SCI favor disease and illness resistance. As opportunistic infections of the urinary tract, lungs, and skin represent major causes of morbidity for those aging with SCI, attention to, or intervention on, immune suppressive states, traits, behaviors, diets, and medications may represent a means through which host defenses of persons with SCI can be fortified and their illness proclivities reduced.

Disease Susceptibility↗
PubMed1999

NMDA induces BDNF expression in the albino rat retina in vivo.

The effect of an intravitreal injection of NMDA on the expression of brain-derived neurotrophic factor (BDNF) in retinal ganglion cells was investigated in rats. Forty-eight hours after intravitreal injection of NMDA retinal ganglion cell BDNF immunoreactivity was practically obliterated, as was the choline acetyltransferase (ChAT) immunoreactivity associated with a subset of amacrine cells. However, 2h following treatment with NMDA the BDNF immunoreactivity and BDNF mRNA associated with the ganglion cells was enhanced while the amacrine cell ChAT immunoreactivity was clearly reduced and the levels of mRNA coding for rhodopsin and Thy-1 did not change. However, 4h after NMDA injection the increase in BDNF mRNA was now no longer apparent. The results show that synthesis of BDNF is increased in the ganglion cells immediately following an insult by NMDA. It is suggested that this is a natural protective mechanism of rat retinal ganglion cells.

Animals↗
PubMed1999

Topically applied betaxolol attenuates NMDA-induced toxicity to ganglion cells and the effects of ischaemia to the retina.

The present results show that topically applied Betoptic(R)(0.5% betaxolol) to the rabbit or rat eye reaches the retina and can counteract the detrimental effects caused by ischaemia/reperfusion or N -methyl- d -aspartate (NMDA)-induced insults to the retina. Betaxolol is a beta(1)-adrenergic blocker but its neuroprotective action is generally thought to be due to its calcium channel blocking properties. Support for this view comes from studies on cultures of cortical neurones where it was found that betaxolol attenuated the NMDA-induced influx of(45)Ca(2+)while beta-adrenoreceptor agonists were ineffective. Topically applied Betoptic(R)to the rabbit eye was observed to reach the retina in maximal amounts within 60 min. Some of the substance was also found in the contralateral retina of the untreated eye suggesting that the agent reaches the retina by local systemic and retinal circulation. Concurrent treatment with Latanoprost(R)did not result in a greater amount of betaxolol reaching the retina. An ophthalmodynamometric procedure, which raises the intraocular pressure, was used to apply an ischaemic insult to the rabbit retina. After three days of reperfusion the b-wave of the electroretinogram was reduced by an average of 59% and the choline acetyltransferase immunoreactivity in the retina was almost obliterated. However, when experiments were carried out on animals which had been treated with one drop of Betoptic(R) twice daily for 4 weeks before ischaemia and also during the reperfusion phase, the reductions in both the b-wave of the electroretinogram and retinal choline acetyltransferase immunoreactivity due to ischaemia/reperfusion were greatly attenuated. Intravitreal injection of NMDA into the rat eye caused a decrease in the immunostaining for Thy-1 antigen which is associated with ganglion cells. The Thy-1 mRNA level was also reduced as was the mRNA for the common subunit of the NMDA receptor, the NR1 subunit. However, in animals subjected to a topical Betoptic(R)regime, before and after intravitreal injection of NMDA, the decreases in the mRNA levels of Thy-1 and NR1 were significantly attenuated.

Administration, Topical↗
PubMed1999

The 5-HT(1A)Receptor agonist 8-OH-DPAT lowers intraocular pressure in normotensive NZW rabbits.

The aims of this study were first to investigate the effect of topical instillation of the 5-HT(1A)receptor agonist 8-OH-DPAT on intraocular pressure (IOP) in normotensive rabbits and second to establish whether the drug reaches the aqueous humour of treated and contralateral eyes at concentrations sufficient to activate ciliary epithelial 5-HT(1A)receptors. Following topical unilateral instillation of (+/-), (+) or (-)8-OH-DPAT, the IOP of rabbits was measured using an applanation tonometer. For the penetration study, [(3)H]8-OH-DPAT was instilled into one eye of each rabbit. Animals were killed after 30 min and the radioactive content of treated and contralateral ocular tissues was assessed. Administration of (+/-)8-OH-DPAT caused dose-dependent decreases in IOP in treated eyes of rabbits during the light and dark. The full 5-HT(1A)agonist (+)8-OH-DPAT was shown to be a more effective hypotensive agent than the partial agonist (-)8-OH-DPAT. The effect of (+/-)8-OH-DPAT on IOP was blocked by pretreatment with pindolol, a mixed 5-HT(1A)antagonist/beta-blocker, but not by the specific beta-blocker betaxolol. After instillation of [(3)H]8-OH-DPAT, peak levels of radioactivity were found in the cornea, followed by similar amounts in the iris-ciliary body and aqueous. There was negligible radioactivity present in tissues of the contralateral eye. This study demonstrates that topical administration of the 5-HT(1A)agonist 8-OH-DPAT dose-dependently decreases IOP in normotensive rabbits during the light and dark. The action of 8-OH-DPAT is presumably local to the anterior uvea as IOP was reduced only in treated eyes and [(3)H]8-OH-DPAT failed to reach the contralateral eye after unilateral instillation. Moreover, since 5-HT(1A)receptors are located in the rabbit ciliary epithelium and the effect of 8-OH-DPAT is blocked by a recognized 5-HT(1A)antagonist, the mechanisms of action of 8-OH-DPAT may well involve a decreased secretion of aqueous humour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Nonselective debridement and antimicrobial cleansing of a venting ductal breast carcinoma.

A woman with a moderately differentiated carcinoma that erupted through the skin and amputated her breast was treated with whirlpool, topical antimicrobials, radiation, and chemotherapy. The draining, necrotic, and septic wound was treated for 5 months with a whirlpool containing dilute povidone-iodine solution and intravenous chemotherapy. Wet bandages, necrotic tissue, and softened eschar were removed by whirlpool agitation or mechanically debrided. To start treatment the wound was dressed with Debrisan crystals and sterile gauze for 1 week. Afterwards, wet-to-dry dressings wetted with Dakin's solution were applied. Tissue ingrowth at the wound margin started after 2 weeks, with whirlpool treatments effecting a tissue-reddening hyperemia. Wound drainage ceased after 2 months, with granulation and revascularization resulting. Eleven months later the wound was closed, aseptic, and undergoing dry flaking. The patient was cancer free with a completely healed wound 2 years after treatment. In this case, nonspecific debridement using whirlpool and topical antimicrobials promoted healing of an open fungating wound from a breast carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Neuroprotection in relation to retinal ischemia and relevance to glaucoma.

Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP isjust an important risk factor in glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result from a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover, experimental studies show that betaxolol is an efficient neuro protective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally.

Adrenergic beta-Antagonists↗