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Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin.

The X-ray crystal structure of the trypsin complex formed with N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-piper idine (NAPAP) was determined with X-ray data to 0.18-nm resolution and crystallographically refined. NAPAP binds into the active site of trypsin in a quite compact form: the p-amidinophenylalanine moiety of the D-stereoisomer binds into the specificity pocket; the glycyl group is hydrogen bonded with Gly216; the naphthyl group stands perpendicular to the indole moiety of Trp215; the piperidine ring is tightly packed between this naphthyl moiety and His57; in consequence the carboxy-terminal amido bond of NAPAP is located in such a way that it is not susceptible to the active-site Ser195. NAPAP and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) [Matzusaki, T., Sasaki, C., Okumura, C. & Umeyama (1989) J. Biochem. (Tokyo) 105, 949-952] were transferred in their trypsin-binding conformations to human alpha-thrombin [Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R. & Hofsteenge, J. (1989) EMBO J. 8. 3467 - 3475] and energy minimized. Both synthetic inhibitors fit perfectly into the much more restricted active site of thrombin. The accommodation of the S-aryl moieties in the 'aryl-binding site' and of the piperidine rings in the S2 subsite of thrombin are particularly favorable. The preference of thrombin for distinctly substituted piperidine derivatives and its generally higher (compared with trypsin) affinity for benzamidine and arginine-based inhibitors can be accounted for by these thrombin inhibitor models.

Animals↗

The new pariahs: discourse on the tobacco industry in the Sydney press, 1993-97.

OBJECTIVE: To review the principal sub-texts contained in all press coverage and references to the tobacco industry in a major Sydney newspaper over five years. METHOD AND SAMPLE: After excluding value-neutral financial page reports, thematic analysis of all value-laden references to the tobacco industry in the Sydney Morning Herald, January 1993 to December 1997. RESULTS: Some 155 articles containing 221 separate references to the tobacco industry were identified. Eight sub-texts (callous merchants of death; conspiracy/cover-up; blood money; toxic pied pipers; corporate leviathans; beleaguered/legitimate industry; index case of unethical or corrupt practice; and bumbling fools) accounted for all 221 references. Eighty-nine per cent of references to the industry framed it negatively. Journalists or regular newspaper columnists authored 56% of the references. Only 5% of comments were attributed to tobacco company sources. CONCLUSIONS: In press reports, the tobacco industry is routinely framed as a corporate pariah by journalists, the public, government spokespeople and tobacco control advocates. IMPLICATIONS: Routine negative publicity about the tobacco industry is likely to significantly reduce its public credibility and political influence.

Humans↗

Fatigue in an older population.

OBJECTIVES: Fatigue is a common symptom that has not been studied well in the older populations. The purpose of this pilot study was to examine the epidemiology of fatigue symptoms in relation to demographic and medical characteristics of older patients in a long-term care setting. DESIGN: A cross-sectional interviewer-assisted survey. PARTICIPANTS/SETTING: A total of 199 ambulatory older residents of a single residential care facility. MEASUREMENTS: Along with medical and demographic characteristics, the survey included mental status (Folstein), activities of daily living (Katz and Lawton), depression (Yesavage GDS), a 3-minute walk, a 7-item pain scale, and the modified Piper Fatigue Scale. RESULTS: One-hundred ninety-nine (65%) of 308 potential subjects completed the study (mean age 88 years, 82% female). Of these 199 subjects, 195 (98%) reported some fatigue symptoms (median duration 44 weeks). Significant (P < .0005) relationships were found between fatigue and GDS (r = 0.57), 3-minute walk (r = -0.29), Lawton IADLs (r = 0.31), pain (r = 0.36), and number of medications (r = 0.26). No significant relationships were found between fatigue and age, sex, Folstein score, or number of medical diagnoses. Multivariate regression analysis identified GDS, pain, number of medications and 3-minute walk as significant predictors of fatigue intensity (multiple R = 0.68, r2 = 0.46, P < .02). CONCLUSIONS: Fatigue is a symptom often found among older residents of a residential facility and has important implications for quality of life. Fatigue is poorly recognized and probably undertreated in older people.

Activities of Daily Living↗

Kava pyrones and resin: studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain.

Kava, an intoxicating beverage prepared from the pepper plant Piper methysticum, is widely consumed by the indigenous peoples in the islands of the South Pacific. As the first of a series of studies on the neuropharmacological interactions of kava with CNS receptors we tested purified pyrones and kava resin for activity on GABA and benzodiazepine binding sites in rat and mouse brain membranes. Only weak activity was observed on GABAA binding sites in washed synaptosomal membranes prepared from rat brain and this was abolished by extraction of the membranes with Triton X-100, suggesting that lipid soluble components were involved. No effects were observed on GABAB binding sites in rat brain membranes in vitro. Kava resin and pyrones exerted some weak effects on benzodiazepine binding in vitro but this did not correlate with pharmacological activity. In addition, in ex vivo studies, no effects were observed on [3H]diazepam binding to brain membranes prepared from mice in which selected kava constituents were injected intraperitoneally, whereas similarly administered diazepam (5 mg/kg) inhibited [3H]diazepam binding by greater than 95%. Similar lack of activity was observed in in vivo binding studies; injection of kava resin failed to influence the CNS binding of the benzodiazepine-receptor ligand [3H]Ro15-1788 injected into mice prior to sacrifice. The pharmacological activities of kava resin and pyrones do not appear to be explained by any significant interaction with GABA or benzodiazepine binding sites.

Animals↗

Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity.

Doxorubicin is an important and effective anticancer drug widely used for the treatment of various types of cancer but its clinical use is limited by dose-dependent cardiotoxicity. Elevated tissue levels of cellular superoxide anion/oxidative stress are a mechanism by which doxorubicin-induced cardiotoxicity. Selected medicinal plant extracts were tested for their antioxidant capacity and cardioprotective effect against doxorubicin-induced cardiotoxicity. The cardiac myoblasts H9c2 were incubated with the antioxidants ascorbic acid, trolox, N-acetylcysteine or selected medicinal plant extracts including; 1) ethanolic extracts from Curcuma longa L-EtOH Phyllanthus emblica L-EtOH, and Piper rostratum Roxb-EtOH; and 2) water extracts from Curcuma longa L-H2O and Morus alba L-H2O. The cardioprotective effects of these extracts were evaluated by crystal violet cytotoxicity assay. IC50s of doxorubicin were compared in the presence or absence of ascorbic acids, trolox, N-acetylcysteine or plant extracts. Morus alba L-H2O showed the highest antioxidant properties evaluated by ferric reducing/antioxidant power assay. Ascorbic acid and N-acetylcysteine had modest effects on the protection of doxorubicin-induced cytotoxicity while trolox showed insignificant protective effect. All plant extracts protected cardiac toxicity at different degrees except that Curcuma longa L-EtOH had no protective effect. Phyllanthus emblica-EtOH (100 microg/ml) showed the highest cardioprotective effect (approximately 12-fold doxorubicin IC50 increase). The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin.

Animals↗

The challenge of evaluating fatigue.

Fatigue, though a common complaint, presents a challenge to nurse practitioners who must evaluate its significance in the primary care setting. Fatigue is described as a multidimensional phenomenon and is classified as physiologic, acute, or chronic. A distinction is made between chronic fatigue and chronic fatigue syndrome (CFS). The use of the Piper Fatigue Scale is suggested in order to objectively quantify this symptom in clinical practice. In this article, the Habit and Lifestyle Form for the Evaluation of Fatigue is presented as a way to assist the provider in considering simple and obvious causes of fatigue that may otherwise be overlooked. Finally, an algorithm for the evaluation of fatigue is presented.

Algorithms↗

Beta-blocker medication usage in older women after myocardial infarction.

PURPOSE: The purpose of this study was to assess demographic characteristics of women prescribed beta-blocker (beta-blocker) medication and compare to those not using beta-blocker medication, and to determine if there are differences in depression and fatigue among women who used beta-blockers compared to nonusers 6-12 months after myocardial infarction (MI). DATA SOURCES: This was a descriptive cross-sectional study of 84 women (61 using beta-blockers and 23 not using beta-blockers) aged 65 and older who were 6-12 months post-MI. Women had their height and weight measured and completed a Demographic Health Form, the Geriatric Depression Scale, and the Revised Piper Fatigue Scale (RPFS). CONCLUSIONS: While most of the women were taking beta-blockers after MI (74%), significantly fewer Black women were taking beta-blockers (chi(2) = 5.086, p = 0.032). Most of the beta-blocker users were overweight or obese. There were no significant differences in age, t(82) = 0.7, p = 0.486; body mass index, t(82) = 0.76, p = 0.445; income, chi(2)(df = 2) = 3.219, p = 0.075; mean depression, t(82) = 1.648, p = 0.103; or fatigue scores, t(82) = 0.993, p = 0.324, between beta-blocker users and nonusers. More of those not taking beta-blockers reported fatigue with significantly higher fatigue in the affective meaning dimension of the RPFS, t(82) = 2.272, p = 0.03. IMPLICATIONS FOR PRACTICE: beta-Blocker medication continues to be underutilized in older women. Because no difference was noted in fatigue and depression in the two groups, these may mean that these side effects are not barriers in prescribing this medication post-MI. Nurse practitioners are in pivotal positions to monitor the ongoing physiological and psychological sequelae post-MI and implement interventions to improve their outcomes.

Adrenergic beta-Antagonists↗

Desmethoxyyangonin and dihydromethysticin are two major pharmacological kavalactones with marked activity on the induction of CYP3A23.

Kava kava (Piper methysticum), an herbal remedy, is widely used for the treatment of mild to moderate cases of anxiety. The therapeutic activity is presumably achieved through multiple constituents called kavalactones. Recently, kava extracts were shown to induce CYP3A4 and activate human pregnane X receptor (PXR). This study was undertaken to test the ability of purified kavalactones to induce CYP3A23 and activate PXR. Rat hepatocytes were treated with desmethoxyyangonin, dihydrokawain, dihydromethysticin, kawain, methysticin, or yangonin, and the expression of CYP3A23 was monitored. Among the kavalactones, only desmethoxyyangonin and dihydromethysticin markedly induced the expression of CYP3A23 (approximately 7-fold). A similar magnitude of induction was detected with combined six kavalactones at a noninductive concentration when individually used. The induced expression, however, was markedly reduced or completely abolished if dihydromethysticin, desmethoxyyangonin, or both were excluded from the mixtures. Interestingly, regardless of whether dihydromethysticin or desmethoxyyangonin was used alone or together with other kavalactones, similar amounts of total kavalactones were needed to produce comparable induction, suggesting that the inductive activity of dihydromethysticin and desmethoxyyangonin is additively/synergistically enhanced by other kavalactones. In addition, treatment with dihydromethysticin, desmethoxyyangonin, or pregnenolone 16alpha-carbonitrile (PCN) markedly increased the levels of CYP3A23 mRNA, and inhibition of mRNA synthesis abolished the induction. In contrast to PCN, dihydromethysticin and desmethoxyyangonin only slightly activated rat or human PXR. These findings suggest that the induction of CYP3A23 by dihydromethysticin and desmethoxyyangonin involves transcription activation, probably through a PXR-independent or PXR-involved indirect mechanism.

Animals↗

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.

Anti-Bacterial Agents↗

Improvement of in vitro and in vivo antileishmanial activities of 2', 6'-dihydroxy-4'-methoxychalcone by entrapment in poly(D,L-lactide) nanoparticles.

The inhibition of intracellular Leishmania amazonensis growth by 2', 6'-dihydroxy-4'-methoxychalcone (DMC) isolated from Piper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.

Animals↗

Responses of Sorghum and Pennisetum Species to the N(2)-Fixing Bacterium Azospirillum brasilense.

Three field inoculation experiments, two in Florida and one in New Mexico, were conducted with Azospirillum brasilense Cd. Each of the Florida experiments evaluated two crop species. One species in each of the Florida experiments responded to inoculation with a significant dry matter yield increases of 11 to 24% and nitrogen yield increases of 9 to 39%. No inoculation response was noted in the New Mexico experiment. The responding species were Sorghum bicolor (L.) Moench (sorghum) and the interspecific hybrid between Pennisetum americanum (L.) K. Schum. (pearl millet) and P. purpureum Schumach. (napiergrass). Nonresponding species were pearl millet (Florida) and Sorghum sudanense (Piper) Staph. (New Mexico). Acetylene reduction activity of inoculated plots in Florida was low, showing no increase over the natural uninoculated background rates and, in one case, was negatively correlated with yield. Acetylene reduction activity was not measured in New Mexico. In Florida, A. brasilense populations were found to decline from 5 x 10 to 5 x 10 bacteria g of soil in about 3 weeks (quadratic regressions). Continued decline to less than 10 by week 5 indicated that the inoculated bacteria did not become established in the soil in high numbers. The A. brasilense population declined at about the same rate in the New Mexico experiment. The erractic inoculation responses in these experiments are similar to those observed in earlier work at the University of Florida. The lack of acetylene reduction activity response to inoculation and the rapid population decline of the inoculated bacteria suggest that N(2) fixation is not the major mechanism causing yield responses after inoculation.

Journal Article↗

Aflatoxin contamination of some common drug plants.

This paper deals with the natural occurrence of aflatoxins in some common drug plants collected from storehouses in Bihar, India. Of 15 samples analyzed, 14 were aflatoxin positive. The highest level of aflatoxin contamination was detected in the seeds of Piper nigrum (1.20 micrograms/g), followed by the level detected in the seeds of Mucuna prurita (1.16 micrograms/g), and the lowest level was detected in the bark of Acacia catechu (0.09 micrograms/g). Of 158 isolates of Aspergillus flavus obtained from as many samples of drug plants, 49 were found to be toxigenic. The amount of aflatoxin B1 elaborated by the toxigenic isolates was in the range of 0.86 to 5.24 micrograms/ml of culture filtrate.

Aflatoxins↗

Genetic and sequence analysis of the pTiC58 trb locus, encoding a mating-pair formation system related to members of the type IV secretion family.

Conjugal transfer of pTiC58 requires two regions, tra which contains the oriT and several genes involved in DNA processing and a region of undefined size and function that is located at the 2-o'clock position of the plasmid. Using transposon mutagenesis with Tn3HoHo1 and a binary transfer system, we delimited this second region, called trb, to an 11-kb interval between the loci for vegetative replication and nopaline catabolism. DNA sequence analysis of this region identified 13 significant open reading frames (ORFs) spanning 11,003 bp. The first, encoding traI, already has been described and is responsible for the synthesis of Agrobacterium autoinducer (AAI) (I. Hwang, P.-L. Li, L. Zhang, K. R. Piper, D. M. Cook, M. E. Tate, and S. K. Farrand, Proc. Natl. Acad. Sci. USA 91:4639-4643, 1994). Translation products of the next 11 ORFs showed similarities to those of trbB, -C, -D, -E, -J, -K, -L, -F, -G, -H, and -I of the trb region of the octopine-type Ti plasmid pTi15955 and of the tra2 core region of RP4. In RP4, these genes encode mating-pair formation functions and are essential for the conjugal transfer of the IncP plasmid. Each of the trb gene homologues is oriented counterclockwise on the Ti plasmid. Expression of these genes, as measured by using the lacZ fusions formed by Tn3HoHo1, required the traI promoter and the transcriptional activator TraR along with its coinducer, AAI. While related to that of RP4, the trb system of pTiC58 did not allow propagation of the trb-specific bacteriophages PRD1, PRR1, and Pf3. The products of several trb genes of the Ti plasmid are similar to those of other loci that encode DNA transfer or protein secretion systems, all of which are members of the type IV secretion family.

Agrobacterium tumefaciens↗

In situ activation of the quorum-sensing transcription factor TraR by cognate and noncognate acyl-homoserine lactone ligands: kinetics and consequences.

Conjugal transfer of Ti plasmids of Agrobacterium tumefaciens is controlled by a quorum-sensing system composed of the transcriptional activator TraR and its acyl-homoserine lactone quormone N-(3-oxo-octanoyl)-L-homoserine lactone (3-oxo-C8-HSL). The population density dependence of quorum-sensing systems can often be circumvented by addition of the quormone to cultures at low cell numbers. However, the quorum-dependent activation of Ti plasmid conjugal transfer exhibited a lag of almost 8 h when the quormone was added to donor cells at low population densities (Piper and Farrand, J. Bacteriol. 182:1080-1088, 2000). As measured by activation of a TraR-dependent traG::lacZ reporter fusion, TraR in cells exposed to the cognate signal for 5 min showed detectable activity, while exposure for 15 min resulted in full activity. Thus, the lag in activation is not due to some intrinsic property of TraR. Cells exposed to the agonistic analog N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) exhibited similar induction kinetics. However, activation of the reporter in cells exposed to the poorly effective alkanoyl acyl-HSL N-hexanoyl-L-homoserine lactone (C6-HSL) required the continued presence of the signal. As measured by an in vivo repressor assay, TraR activated by 3-oxo-C6-HSL or by 3-oxo-C8-HSL remained active for as long as 8 h after removal of exogenous signal. However, TraR activated by the alkanoyl quormone C6-HSL rapidly lost activity following removal of the signal. In quormone retention assays, which measure signal binding by TraR, cells grown with either of the two 3-oxo-acyl-HSL quormones retained the ligand after washing, while cells grown with C6-HSL lost the alkanoyl-HSL concomitant with the rapid loss of TraR activity. We conclude that TraR rapidly binds its quormone and that, once bound, the cognate signal and its close homologs are tightly retained. Moreover, in the absence of other regulatory factors, activated TraR remains functional after removal of the signal. On the other hand, poorly active signals are not tightly bound, and their removal by washing leads to rapid loss of TraR activity.

4-Butyrolactone↗

Acupressure and Transcutaneous Electrical Acupoint Stimulation in improving fatigue, sleep quality and depression in hemodialysis patients.

The purpose of this study was to test the effectiveness of acupressure and Transcutaneous Electrical Acupoint Stimulation (TEAS) on fatigue, sleep quality and depression in patients who were receiving routine hemodialysis treatment. The study was a randomized controlled trial; qualified patients were randomly assigned to acupressure, TEAS or control groups. Patients in the acupressure and TEAS groups received 15 minutes of treatment 3 times a week for 1 month, whereas patients in the control group only received routine unit care. A total of 106 patients participated in the study. Methods of measurement included the revised Piper Fatigue Scale (PFS), the Pittsburgh Sleep Quality Index and the Beck Depression Inventory. Data were collected at baseline, during the intervention and post-treatment. The results indicated that patients in the acupressure and TEAS groups had significantly lower levels of fatigue, a better sleep quality and less depressed moods compared with patients in the control group based upon the adjusted baseline differences. However, there were no differences between acupressure and TEAS groups in outcome measures. This study provides an alternative method for health care providers in managing dialysis patients with symptoms of fatigue, poor sleep or depression.

Acupressure↗

Effects of aqueous extracts of "Betel quid" and its constituents on testosterone production by dispersed mouse interstitial cells.

Betel quid (BQ) is a favorite chewing item among many communities in different parts of Asia where it is popular by different names. BQ is a unique combination of nut or fruit from the Areca catechu Linn. (AN) tree, leaf from the Piper betle Linn. (BL) vine, slaked lime, paste of bark from the Acacia catechu tree and other spices. AN has been used successfully in various traditional medicines by different civilizations over several ages. Initially condemned by the medical communities for its health hazards, identification and application of potent pharmacologically bioactive compounds from different constituents of BQ have rekindled growing interest in related investigations. Curious about the stimulating role of BQ, we investigated the potential steroidogenic activity of hot water extract from BQ and its constituents and arecoline on testosterone producing ability in an in vitro experiment. Enzyme dissociated interstitial cells from adult mouse testes (ICR strain) were cultured with/without different doses of the extracts and the level of testosterone produced was assayed by an enzyme immunoassay (EIA) technique. It was found that at lower doses of arecoline, AN and BL extracts had significantly stimulated testosterone production over the basal level (p < 0.05). BQ extract, on the other hand, did not show any significant effect on testosterone production. Combinations of arecoline at low doses with 10 ng/ml ovine leutinizing hormone (oLH) showed increases in testosterone produced, while cyclic adenosine monophosphate (cAMP) co-culture showed dose-related inhibition. Our current finding hints at the possible dose-dependent dualistic role of AN and BL extracts and arecoline for testosterone production employing possible non-cAMP-dependent pathway of steroidogenesis. However, the identity of the active compounds besides arecoline and the exact mechanism involved remains to be further investigated.

Animals↗

Antibacterial activity of alimentary plants against Staphylococcus aureus growth.

Alimentary plants were screened for antibacterial activity against a penicillin G resistant strain of Staphylococcus aureus. Twenty-five samples of plant material corresponding to 21 species from 13 families were used. Both aqueous and ethanol extracts were obtained from them. Antibacterial activity was determined by the agar-well diffusion method, using cephazolin as a standard antibiotic. Seventeen ethanol extracts were found active. Eugenia caryophyllata (clavo de olor*) flowers, Myristica fragans (nuez moscada*) seeds, Theobroma cacao (cacao*) seed bark, Triticum sp (trigo*) fruit, Zea mays (maíz*) fruit and Piper nigrum (pimienta*) ripe fruit produced some of the more active extracts (* = Argentine vulgar names).

Cefazolin↗

Spatial properties of photophobia.

PURPOSE: To determine the spatial properties of stimuli that elicit photophobia (PP) in normal subjects: Does PP exhibit spatial summation? Are different parafoveal quadrants (superior, inferior, temporal, and nasal) of the retina differentially sensitive in PP? What is the relationship between PP sensitivity and retinal eccentricity? What is the relationship between the spatial properties of PP and the spatial distribution of macular pigment (MP)? METHODS: A Maxwellian-view optical system with a xenon light source was used to present the stimuli. Four normal subjects viewed stimuli of various sizes, retinal locations, and one of two chromatic contents: xenon-white and a broadband orange. The intensity of the test stimulus was increased between trials until the PP threshold was reached. The squinting response corresponding to PP was assessed by electromyography and used as an objective criterion of PP. Three parameters were examined: stimulus size, parafoveal retinal locus (superior, inferior, temporal, and nasal), and retinal eccentricity (extending into the perifovea). Spatial profiles of MP were measured psychophysically using heterochromatic flicker photometry (HFP). RESULTS: Spatial summation for PP was found essentially to adhere to Piper's law (radiance proportional to square root of stimulus area). The PP response was greater to centrally than peripherally viewed targets. In this regard, MP acted as a spatially integrated filter in the attenuation of PP. CONCLUSIONS: The degree of spatial summation found for PP indicates that an increase of 1.0 log unit in field area results in an approximately 0.57-log-unit decrease in the radiance required to elicit PP. PP appears to serve the function of retinal photoprotection.

Adult↗