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S Padilla

Publications and source records attributed to S Padilla.

At least 91 records · Page 5Linked to original sources
PubMed1993

Relationship of neuropathy target esterase inhibition to neuropathology and ataxia in hens given organophosphorus esters.

Adult White Leghorn hens were acutely exposed to 3 dosages of the following organophosphorus compounds: mipafox, tri-ortho-tolyl phosphate (TOTP), phenyl saligenin phosphate, and diisopropylphosphorofluoridate (DFP). Neuropathy target esterase (NTE) activity was measured in brain and spinal cord 4 or 48 h after exposure. Ataxia was assessed using an 8-point rating scale on days 9 through 21 after administration, and neuropathological examination was conducted on samples collected from perfusion-fixed animals on day 21. Morphological alterations were indicated by lesion scores between 0 (no lesions) and 4 (diffuse involvement of spinal cord tracts and > 25% degeneration of peripheral nerve fibers). Dosages of mipafox (30 mg/kg i.p.), TOTP (500 mg/kg p.o.), phenyl saligenin phosphate (2.5 mg/kg i.m.) and DFP (1 mg/kg s.c.) that were capable of inhibiting NTE > 80% in both brain and spinal cord preceded ataxia which reached maximal levels (scores of 7-8), and development of lesions scored as 4. Hens were notably impaired (ataxia scores of 3-4) 21 days after administration of dosages of mipafox (3 and 6 mg/kg), TOTP (90 mg/kg), phenyl saligenin phosphate (0.1 and 0.2 mg/kg), and DFP (0.4 mg/kg) when spinal cord NTE was inhibited 40-75%. Lesions were, however, only noted in spinal cord and peripheral nerves of hens given TOTP or DFP (scores 1-3). These data indicate that inhibition of spinal cord NTE > 80% was predictive of severe ataxia and extensive pathology in the hen and that less NTE inhibition was indicative of less severe ataxia and a lower score for neuropathological damage.

Animals↗
PubMed1993

An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia.

In 1989, our medical center used continuous quality improvement concepts in the creation of a Nosocomial Pneumonia Prevention Team whose aim was to significantly reduce nosocomial ventilator-associated pneumonia. The team included representatives from nursing, respiratory therapy, pulmonary medicine, internal medicine, anesthesiology, education and training, and infection control. Because the majority of mechanically ventilated patients were located in the intensive care unit, this unit became the focus of the prevention efforts. Team meetings were held regularly, with all representatives brainstorming barriers, possible interventions, methods of outcome measurement, and frequency of evaluation. Policies and procedures were reviewed, surveillance was increased, handwashing practices were surveyed, periodic feedback to staff was begun, and an educational program was developed and presented. During 1990, we observed a 57% reduction in ventilator-associated pneumonia from the baseline years, 1987 and 1988. Statistical comparison of proportions by z test indicated a p value less than 0.05. Fifteen cases of nosocomial ventilator-associated pneumonia were prevented and a cost saving of $105,000 was realized. Performance of traditional surveillance for outliers, coupled with literature-based thresholds, can lead to tolerance of inordinately high endemic rates. Infection control programs can significantly reduce endemic rates of nosocomial ventilator-associated pneumonia through continuous quality improvement methods and multidisciplinary interventions, with standard infection control procedures used for improvement.

California↗
PubMed1993

Direct measurement of fast axonal organelle transport in the sciatic nerve of rats treated with acrylamide.

The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. We report the first direct evaluation of the effects of subchronic acrylamide dosing (150, 300, or 500 mg/kg total dose, i.e., 50 mg/kg, 2x/wk, for 1.5, 3, 5 wk, respectively) on the fast axonal transport motility machinery itself using video-enhanced differential interference contrast optics with digital image processing and computer analysis. Four principle observations were made: (1) Rapid anterograde transport was not affected at any dosage level within 1 wk after cessation of dosing. (2) A high cumulative dosage (500 mg/kg total) of acrylamide or bisacrylamide produced approximately 7-18% decrease in the rate of retrograde transport in both myelinated and unmyelinated axons. (3) Lower dosages of acrylamide (150 or 300 mg/kg total) produced an increase in retrograde transport rates in myelinated axons only. (4) During the "recovery" phase for the 500 mg/kg acrylamide animals (i.e., 3 or 5 wk after the last dosage of acrylamide) the rate of anterograde transport in the myelinated axons was decreased at 3 wk but not at 5 wk, and the rate of retrograde transport in the myelinated axons returned to control levels while the retrograde transport in the unmyelinated axons continued at abnormally slow speeds. The application of this new technique to evaluate the neurotoxic effects of acrylamide provides evidence of dynamic changes in the axonal transport motility machinery itself and differential effects on myelinated versus unmyelinated fibers.

Acrylamide↗
PubMed1993

Locally synthesized phosphatidylcholine, but not protein, undergoes rapid retrograde axonal transport in the rat sciatic nerve.

Retrograde axonal transport of phosphatidylcholine in the sciatic nerve has been demonstrated only after injection of lipid precursors into the cell body region. We now report, however, that after microinjection (1 microliter) of [methyl-3H]choline chloride into the rat sciatic nerve (35-40 mm distal to the L4 and L5 dorsal root ganglia), time-dependent accumulation of 3H-labeled material occurred in dorsal root ganglia ipsilateral, but not contralateral, to the injection site. The level of radioactivity in the ipsilateral dorsal root ganglia was minimal at 2 h after isotope injection but was significantly increased at 7, 24, 48, and 72 h after intraneural isotope injection (n = 3-8 per time point); at these time points, all of the radiolabel in the chloroform/methanol extract of the ipsilateral dorsal root ganglia was present in phosphatidylcholine. The radioactivity in the water-soluble fraction did not show a time-dependent accumulation in the ipsilateral dorsal root ganglia as compared with the contralateral DRGs, ruling out transport or diffusion of precursor molecules. In addition, colchicine injection into the sciatic nerve proximal to the isotope injection site prevented the accumulation of radiolabel in the ipsilateral dorsal root ganglia. Therefore, this time-dependent accumulation of radiolabeled phosphatidylcholine in the ipsilateral dorsal root ganglia is most likely due to retrograde axonal transport of locally synthesized phospholipid material. Moreover, 24 h after injection of both [3H]choline and [35S]-methionine into the sciatic nerve, the ipsilateral/contralateral ratio of radiolabel was 11.7 for 3H but only 1.1 for 35S, indicating that only locally synthesized choline phospholipids, but not protein, were retrogradely transported.

Animals↗
PubMed1993

Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina.

Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP.

Aging↗
PubMed1993

Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase.

The preponderance of studies of tolerance to organophosphate (OP) cholinesterase (ChE) inhibitors indicates that functional recovery accompanies neurochemical compensations for the inhibited enzyme. Contrary to prediction, rats dosed with the OP diisopropylfluorophosphate (DFP) showed progressive and persistent impairment of cognitive and motor function over a 3-week period of daily exposure, despite neurochemical and pharmacological evidence of tolerance to its inhibition of ChE. To determine whether these functional effects of DFP resulted from inhibition of ChE and downregulation of muscarinic cholinergic receptors, rats were dosed with chlorpyrifos (CPF), an OP pesticide which inhibits blood and brain ChE of rats for weeks after a single injection. Long-Evans rats were trained to perform an appetitive test of memory and motor function and were then injected s.c. with 0, 60, 125 or 250 mg/kg of CPF in peanut oil and tested 5 days/week for 7 weeks. Unconditioned behavior was also rated for signs of cholinergic toxicity. CPF inhibited ChE activity in whole blood in a dose-related manner for more than 53 days. The degree and time course of ChE inhibition in blood and brain and the downregulation of muscarinic receptors in brain after 125 mg/kg of CPF closely paralleled the previously reported effects of 25 daily injections of 0.2 mg/kg of DFP. In addition, CPF-treated rats were subsensitive to oxotremorine-induced hypothermia for at least 32 days after CPF. However, functional deficits (in working memory and motor function) appeared within 2 days after injection of CPF and recovered within 3 weeks, long before ChE activity and receptor density returned to control levels. Thus, the effects of CPF were neither progressive nor as persistent as those seen during daily DFP injections. This difference suggests that the DFP-induced behavioral changes observed previously cannot be attributed entirely to its effects on ChE activity and changes in [3H]quinuclidinyl benzilate binding.

Animals↗
PubMed1992

Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport.

Human exposure to organic solvents is often complicated by ethanol ingestion and the literature is replete with demonstrations of metabolic interactions between ethanol and organic solvents at a pharmacokinetic level. Because of the possible modulation of xylene toxicity by ethanol consumption, the present group of studies characterizes the effect of ethanol on the p-xylene-induced decrease in axonal transport in the rat optic system previously reported by our laboratory. Long-Evans, hooded, male rats were divided randomly into two groups: those receiving 10% ethanol in their drinking water and those receiving water only. These two groups were further subdivided into two groups which were either exposed by inhalation to 1600 ppm p-xylene for 6 h/day, 5 days/week for 8 exposure-days or were treated identically except that they were exposed to air while in the inhalation chambers. The ethanol-drinking rats were given ethanol 6 days prior to and on the days of the inhalation exposure. Immediately after removal from the inhalation chambers on the last exposure day, the animals were injected intraocularly with [35S]methionine and [3H]fucose to measure the synthesis and rapid axonal transport of proteins and glycoproteins, respectively, in the retinal ganglion cells. The animals were sacrificed 20 h later, and the amount of radioactivity in different areas of the retinal ganglion cells was determined by liquid scintillation counting. As in previous experiments, the xylene exposure group showed a significant reduction in axonal transport of proteins and glycoproteins, whereas the ethanol exposure alone produced no significant reductions in the transport of either proteins or glycoproteins. In the animals receiving both ethanol and xylene, however, the ethanol treatment prevented the decreased transport characteristic of the xylene only animals, i.e. in all areas of the optic projections the level of transport were similar to the level present in the control groups. These data suggest that the xylene-induced reduction in rapid axonal transport was reversed (or prevented) by subacute ethanol consumption.

Alcohol Drinking↗
PubMed1992

Physiological correlates of middle-distance running performance. A comparative study between men and women.

To compare the relative contributions of their functional capacities to performance in relation to sex, two groups of middle-distance runners (24 men and 14 women) were selected on the basis of performances over 1500-m and 3000-m running races. To be selected for the study, the average running velocity (v) in relation to performances had to be superior to a percentage (90% for men and 88% for women) of the best French v achieved during the season by an athlete of the same sex. Maximal O2 consumption (VO2max) and energy cost of running (CR) were measured in the 2 months preceding the track season. This allowed us to calculate the maximal v that could be sustained under aerobic conditions, va,max. A v:va,max ratio derived from 1500-m to 3000-m races was used to calculate the maximal duration of a competitive race for which v = va,max (tva,max). In both groups va,max was correlated to v. The relationships calculated for each distance were similar in both sexes. The CR [0.179 (SD 0.010) ml.kg-1 x m-1 in the women versus 0.177 (SD 0.010) in the men] and tva,max [7.0 (SD 2.0) min versus 8.4 (SD 2.1)] also showed no difference. The relationships between VO2max and body mass (mb) calculated in the men and the women were different. At the same mb the women had a 10% lower CR than the men; their lower mb thus resulted in an identical CR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase.

The role of blood acetylcholinesterase in moderating the effects of organophosphate challenge in rats was tested. Adult male rats (n = 42) were injected (iv) either with monoclonal antibodies (MAb) to rat acetylcholinesterase (EC 3.1.1.7; AChE) or normal mouse IgG (controls). Two days later, the rats were injected (sc) with either a mild (0.17 mg/kg) or moderate dosage (0.34 mg/kg) of paraoxon or with vehicle. Neurological integrity was assessed by a functional observational battery followed by motor activity, 3 to 4 hr after dosing. Blood, brain, and diaphragm tissues were then collected for determination of AChE activity. MAb treatment reduced whole blood and plasma AChE activity by 32 and 90%, respectively, but did not affect neurobehavioral parameters or the AChE activity of brain or diaphragm. The paraoxon challenge produced dose-related neurobehavioral changes and inhibition of brain and diaphragm AChE activity to the same extent in IgG- and MAb-treated rats. Thus, significant loss in blood AChE alone produced no detectable neurobehavioral deficits and did not alter the subsequent responses to paraoxon challenge.

Acetylcholinesterase↗
PubMed1992

Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals.

The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age-related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development.

Animals↗
PubMed1991

Murine susceptibility to organophosphorus-induced delayed neuropathy (OPIDN).

This study reports that CD-1 strain mice are neuropathologically and biochemically responsive to acute doses of tri-ortho-cresyl phosphate (TOCP). Young (25-30 g) male and female animals were exposed (po) to a single dose of TOCP (580-3480 mg/kg) and sampled for neurotoxic esterase (NTE) activity at 24 and 44 hr postexposure and for neuropathic damage 14 days later. Biochemically, high intragroup variability existed at the lower doses, and at higher levels of TOCP exposure (i.e., greater than or equal to 1160 mg/kg), mean brain NTE inhibition never exceeded 68%. Hen and mouse brain NTE activity, assayed in vitro for sensitivity to inhibition by tolyl saligenin phosphate (TSP), the active neurotoxic metabolite of TOCP, showed similar IC50 values. Histologically, highly variable spinal cord damage was recorded throughout treatment groups and mean damage scores followed a dose-response pattern with no apparent correlation to threshold (i.e., greater than or equal to 65%) inhibition of brain NTE activity. Topographically, axonal degeneration in the mouse spinal cord predominated in the lateral and ventral columns of the upper cervical cord. Unlike the rat, which displays degeneration in the upper cervical cord's dorsal columns (i.e., gracilis fasciculus) in response to TOCP intoxication, treated mice showed minimal damage to this tract. To examine this discrepancy further, ultrastructural morphometric analysis of axon diameters in the cervical cord was performed in control mice and rats. These results indicated that in both species, the largest diameter (greater than or equal to 4 microns) axons are housed in the ventral columns of the cervical spinal cord, suggesting that axon length and diameter may not be the only criteria underlying fiber tract vulnerability in OPIDN.

Animals↗
PubMed1991

Retrograde axonal transport of locally synthesized phosphoinositides in the rat sciatic nerve.

Although autoradiography has demonstrated local incorporation of [3H]inositol into axonal phospholipids after intraneural injection, retrograde axonal transport of phosphatidylinositol has only been demonstrated after injection of lipid precursor into the cell body regions (L4 and L5 dorsal root ganglia) of the sciatic nerve. We now report the retrograde axonal transport of inositol phospholipids synthesized locally in the axons. Following microinjection of myo-[3H]inositol into the rat sciatic nerve (50-55 mm distal to L4 and L5 dorsal root ganglia), a time-dependent accumulation of 3H label occurred in the dorsal root ganglia ipsilateral to the injection site. The ratio of dpm present in the ipsilateral dorsal root ganglia to that in the contralateral dorsal root ganglia was not significantly different from unity between 2 and 8 h following isotope injection but increased to 10-12-fold between 24 and 72 h following precursor injection. By 24 h following precursor injection, the ipsilateral/contralateral ratio of the water-soluble label in the dorsal root ganglia still remained approximately 1.0, whereas the corresponding ratio in the chloroform/methanol-soluble fraction was approximately 20. The time course of appearance of labeled lipids in the ipsilateral dorsal root ganglia after injection of precursor into the nerve at various distances from the dorsal root ganglia indicated a transport rate of at least 5 mm/h. Accumulation of label in the dorsal root ganglia could be prevented by intraneural injection of colchicine or ligation of the sciatic nerve between the dorsal root ganglia and the isotope injection site. These results demonstrate that inositol phospholipids synthesized locally in the sciatic nerve are retrogradely transported back to the nerve cell bodies located in the dorsal root ganglia.

Animals↗
PubMed1990

Potentiation of organophosphorus-induced delayed neurotoxicity by phenylmethylsulfonyl fluoride.

It is well known that pretreatment with the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF) can protect experimental animals from organophosphorus-induced delayed neurotoxicity (OPIDN), presumably by blocking the active site of neurotoxic esterase (NTE) such that binding and "aging" of the neuropathic OP is thwarted. We report here that while PMSF (60 mg/kg, sc) given 4 h before the neuropathic organophosphate (OP) mipafox (50 mg/kg, im) completely prevented the clinical expression of OPIDN in hens, the identical PMSF treatment markedly amplified the delayed neurotoxicity (relative to hens treated with OP only) if administered 4 h after mipafox (5 or 50 mg/kg, im). Moreover, in a separate experiment using diisopropylphosphorofluoridate (DFP) as the neurotoxicant in place of mipafox, posttreatment with PMSF 4 h after DFP (0.5 mg/kg) also accentuated the severity of ataxia. These data indicate that PMSF only protects against OPIDN if given prior to exposure to the neurotoxicant; treatment with PMSF after OP exposure critically exacerbates the delayed neurotoxicity from exposure to organophosphorus compounds.

Animals↗
PubMed1990

The aesthetic alliance: nurses and medical facials.

This article introduces and explains methods for integrating services of dermatology nurses and cosmetic dermatologists. Basic aesthetic techniques can be incorporated into the dermatology practice; or a specialist, namely a licensed aesthetician, can perform the medical facial.

Acne Vulgaris↗
PubMed1990

Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome. A case report and review of the literature.

Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome is rare; to our knowledge, only four previous cases have been reported. We report a unique case of transfusion-associated acquired immunodeficiency syndrome in a 74-year-old woman. At autopsy, both lungs were extensively affected by Kaposi's sarcoma, Pneumocystis carinii, and cytomegalovirus infection. These three processes led to respiratory failure and accounted for her death.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Modulation of neurotoxic esterase activity in vitro by phospholipids.

Neurotoxic esterase (NTE), the proposed molecular site for the initiation of organophosphorus-induced delayed neuropathy, is a membrane-associated enzyme. NTE activity was solubilized from chicken brain microsomal membranes with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate and partially separated from other solubilized hen brain esterases by DEAE-Sephacel anion-exchange chromatography using stepwise increases in salt concentration; however, there was poor recovery of NTE activity and only a slight increase in NTE specific activity. NTE activity in the "high salt" fraction (i.e., the NTE-enriched fraction) was markedly activated by a heat-stable factor(s) present in other fractions eluted from the column. This activating factor was extracted with organic solvents, suggesting that it may be lipid. In a related study, purified phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were also found to activate the partially separated NTE activity in a concentration-dependent manner while phosphatidyl-inositol was found to inhibit the same partially separated NTE fraction in a concentration-dependent manner. The results suggest that lipids may modulate NTE activity and that the loss of lipid cofactors during chromatographic separations may underlie some of the difficulties encountered in isolation of active NTE.

Animals↗
PubMed1988

Comparison of incremental and steady state tests of endurance training.

To compare the results obtained by incremental or constant work load exercises in the evaluation of endurance conditioning, a 20-week training programme was performed by 9 healthy human subjects on the bicycle ergometer for 1 h a day, 4 days a week, at 70-80% VO2max. Before and at the end of the training programme, (1) the blood lactate response to a progressive incremental exercise (18 W increments every 2nd min until exhaustion) was used to determine the aerobic and anaerobic thresholds (AeT and AnT respectively). On a different day, (2) blood lactate concentrations were measured during two sessions of constant work load exercises of 20 min duration corresponding to the relative intensities of AeT (1st session) and AnT (2nd session) levels obtained before training. A muscle biopsy was obtained from vastus lateralis at the end of these sessions to determine muscle lactate. AeT and AnT, when expressed as % VO2max, increased with training by 17% (p less than 0.01) and 9% (p less than 0.05) respectively. Constant workload exercise performed at AeT intensity was linked before training (60% VO2max) to a blood lactate steady state (4.8 +/- 1.4 mmol.l-1) whereas, after training, AeT intensity (73% VO2max) led to a blood lactate accumulation of up to 6.6 +/- 1.7 mmol.l-1 without significant modification of muscle lactate (7.6 +/- 3.1 and 8.2 +/- 2.8 mmol.kg-1 wet weight respectively). It is concluded that increase in AeT with training may reflect transient changes linked to lower early blood lactate accumulation during incremental exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗