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PubMed2001

Factors determining convalescence after uncomplicated laparoscopic cholecystectomy.

HYPOTHESIS: Detailed information on duration and limiting factors for convalescence after uncomplicated laparoscopic cholecystectomy is lacking. Duration of convalescence may be associated with patients' expectations, given recommendations, and postoperative complaints such as pain and fatigue. DESIGN: Prospective, descriptive study. SETTING: A university hospital. PATIENTS: Two hundred consecutive patients who underwent uncomplicated elective laparoscopic cholecystectomy. INTERVENTION: For sedentary, light, or moderate workload or main recreational activity, we recommended 2 days of postoperative convalescence; for strenuous workload or recreational activity, we recommended 1 week. MAIN OUTCOME MEASURES: Duration and reasons for absence from work. RESULTS: Convalescence from work (n = 85) and recreational activity (n = 198) was 6 days (range, 0-28 days) and 2 days (range, 0-24 days), respectively, in patients recommended for 2 days' convalescence. In patients recommended for 1 week of convalescence, convalescence from work (n = 25) was 10 days (range, 0-52 days), and convalescence from main recreational activity (n = 2), 8 days (range, 5-11 days). Among 87 patients who resumed work or activity later than recommended, pain was a contributory cause in 41 patients, fatigue in 35 patients, and convalescent period falling on a weekend in 26 patients, while 29 patients had arranged vacation or sick leave preoperatively. Preoperative expectation of convalescence and pain were independent contributory factors (P<.01) for convalescence from work for longer than 2 days in patients recommended for 2 days' convalescence. CONCLUSIONS: The period of convalescence after uncomplicated laparoscopic cholecystectomy is about 1 week from work and 2 days from recreational activity when 2 days of convalescence is recommended. Improved pain relief and patient information may further reduce convalescence.

Adult↗
PubMed2006

Interns' compliance with accreditation council for graduate medical education work-hour limits.

CONTEXT: Sleep deprivation is associated with increased risk of serious medical errors and motor vehicle crashes among interns. The Accreditation Council for Graduate Medical Education (ACGME) introduced duty-hour standards in 2003 to reduce work hours. OBJECTIVE: To estimate compliance with the ACGME duty-hour standards among interns. DESIGN, SETTING, AND PARTICIPANTS: National prospective cohort study with monthly Web-based survey assessment of intern work and sleep hours using a validated instrument, conducted preimplementation (July 2002 through May 2003) and postimplementation (July 2003 through May 2004) of ACGME standards. Participants were 4015 of the approximately 37 253 interns in US residency programs in all specialties during this time; they completed 29 477 reports of their work and sleep hours. MAIN OUTCOME MEASURE: Overall and monthly rates of compliance with the ACGME standards. RESULTS: Postimplementation, 1068 (83.6%; 95% confidence interval [CI], 81.4%-85.5%) of 1278 of interns reported work hours in violation of the standards during 1 or more months. Working shifts greater than 30 consecutive hours was reported by 67.4% (95% CI, 64.8%-70.0%). Averaged over 4 weeks, 43.0% (95% CI, 40.3%-45.7%) reported working more than 80 hours weekly, and 43.7% (95% CI, 41.0%-46.5%) reported not having 1 day in 7 off work duties. Violations were reported during 3765 (44.0%; 95% CI, 43.0%-45.1%) of the 8553 intern-months assessed postimplementation (including vacation and ambulatory rotations), and during 2660 (61.5%; 95% CI, 60.0%-62.9%) of 4327 intern-months during which interns worked exclusively in inpatient settings. Postimplementation, 29.0% (95% CI, 28.7%-29.7%) of reported work weeks were more than 80 hours per week, 12.1% (95% CI, 11.8%-12.6%) were 90 or more hours per week, and 3.9% (95% CI, 3.7%-4.2%) were 100 or more hours per week. Comparing preimplementation to postimplementation responses, reported mean work duration decreased 5.8% from 70.7 (95% CI, 70.5-70.9) hours to 66.6 (95% CI, 66.3-66.9) hours per week (P<.001), and reported mean sleep duration increased 6.1% (22 minutes) from 5.91 (95% CI, 5.88-5.94) hours to 6.27 (95% CI, 6.23-6.31) hours per night (P<.001). However, reported mean sleep during extended shifts decreased 4.5%, from 2.69 (95% CI, 2.66-2.73) hours to 2.57 (95% CI, 2.52-2.62) hours (P<.001). CONCLUSION: In the first year following implementation of the ACGME duty-hour standards, interns commonly reported noncompliance with these requirements.

Adult↗
PubMed1996

Streaming conjunctiva.

BACKGROUND: Epithelial proliferation is linked with cell displacement. When a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location that has to be vacated first by peripheral cells. As cells are neither pushed nor pulled in a mechanical sense, and since they do not move by their own means, this displacement is best regarded as streaming. The purpose of the present study was to measure epithelial cell streaming in adult rat conjunctiva. METHODS: Twenty-seven female adult rats were injected i.p. with 18.5 KBq [3H]-thymidine/g body weight, specific activity 185 GBq/mMol. Three rats were killed at different times up to 28 d. Eyes and eyelids were removed in one piece, cut along the pupillary-optic nerve line into 5-microns-thick sections, and prepared for autoradiography. In each eye, the entire upper conjunctiva extending from limbus to the palpebral muco-cutaneous junction was scanned with an ocular micrometer grid. The limbus served as point of origin. The x, y coordinate of each nucleus with two grains or more and its grain content were recorded. RESULTS: One hour after labeling, labeled cells were spread evenly along the basal layer. Cells of the upper layers were not labeled. As time passed by, labeled cells in the fornix became more abundant, while in the limbus and palpebral margin, their frequency declined. Labeled cells streamed from the limbus and palpebral muco-cutaneous junction to the fornix. Bulbar conjunctival epithelia streamed at a velocity of 13.2 microns/day. Epithelia in the palpebral conjunctiva streamed at a velocity of 11.8 microns/day. At the same time cells streamed from the basal layer to the epithelial surface at a velocity of 0.4 microns/day. Generation time was 3.9 days. CONCLUSIONS: Bulbar and palpebral conjunctivae are two independent cell kinetic systems that originate in two stem cell regions, one in the limbus and the other in the muco-cutaneous junction. Each system is made of two compartments, a progenitor where cells proliferate, and a compartment of non proliferating end cells. Progenitors created in the first, enter the second and turn into end cells. Ultimately they die in the fornix. The undetermined limbus stem cell generates two epithelial cell lines, a corneal and a conjunctival.

Animals↗
PubMed1996

Intraalveolar bubbles and bubble films: II. Formation in vivo through adulthood.

BACKGROUND: Intraalveolar bubbles and bubble films have been shown to be part of the normal alveolar architecture in vivo from birth through the first 2 days of extrauterine life of rabbit pups (Scarpelli et al., 1996a. Anat. Rec. 244:344-357). The intraluminal boundary between air-way free gas and alveolar bubbles at the level of respiratory bronchioles is established within 1 hour after birth. We now examine the lung through the rest of development, namely, 2 weeks, 1, 2, and 3 months, and adulthood. METHODS: In quick succession in anesthetized spontaneously breathing rabbits, the abdominal aorta was transected and trachea was occluded either after an end-tidal exhalation at functional residual capacity (FRC) or after volume expansion in vivo by a single inflation from FRC to 20 or 25 cm H2O pressure (V20, V25). Immediately the thorax was opened and lungs were examined (anterior, anterolateral) through a dissecting stereomicroscope while still in the chest, unperturbed (pleural surface temperature 34 degrees C). Heart and lungs were then removed en bloc and re-examined (anterior, lateral, posterior) to confirm that architecture had not changed (22-27 degrees C). After these immediate examinations, lungs were entered into one of the protocols enumerated in Results. RESULTS: Immediate examination revealed bubbles in all aerated subpleural and deep ("central") alveoli from apex to base at all ages and temperatures. Bubbles were confirmed from two views (top and tangential) and from their individual mobility in response to gentle microprobe pressure. A "common bubble" (> 30 microns to approximately 120 microns inside diameter at FRC) appeared to occupy a single alveolus, sometimes arranged in clusters and collectively accounting for approximately 84% of the total bubble population. Few "large bubbles" appeared to be intraductal. We concluded that "small bubbles" (< or = 30 microns; approximately 16% of the total population) were contracted common bubbles. The free gas-bubble film boundary of the airways was at the level of respiratory bronchioles. Subsequent protocols: (1) Common bubbles moved out of adjoining tissue following subpleural incision. Adjacent bubbles either moved into vacated spaces or into the outside liquid medium. Large bubble(s) followed common bubbles out of the tissue. Small bubbles were less mobile and distal common bubbles did not move. The sequence of bubble movement at V25 was the same. Isolated bubbles had normal surfactant content and surface tension according to "Pattle's stability ratio." Transection revealed analogous conditions in central alveoli. (2) Bubble size increased during inflation from FRC to V25. Airless spaces were aerated with bubbles during inflation. (3) The bubble surface was compressed during deflation to 81% of maximal volume (Vmax) and below, including deflation to minimal volume (Vmin). (4) Bubble/alveolar shape changed from spherical-oval to polygonal when the pleural surface dried at FRC and V25. The original shape was restored when the surface was re-wet. Dry tissue showed but did not emit bubbles when cut; re-wet tissue did. (5) Lung liquid content and volume-pressure were normal at FRC. (6) As expected, conventionally fixed, dehydrated, and embedded sections showed no bubbles. CONCLUSIONS: Bubbles and bubble films are fundamental to normal architecture of aerated alveoli at all lung volumes from birth through adulthood. As infrastructure, they sustain aeration and resist deformation. With ductal films, they may be expected to form an alveolar surface liquid (foam film) network (Scarpelli, 1988. Surfactants and the Lining of the Lung) that modulates liquid balance principally at Plateau borders. They expand and contract respectively during inflation and deflation, maintaining their closed film integrity. Films are compressed to "film collapse" in situ during deflation from volumes well above FRC to Vmin. At these volumes, intact films sustain aeration; some may disperse into t

Age Factors↗
PubMed1998

The alveolar surface network: a new anatomy and its physiological significance.

UNLABELLED: It is generally held that the terminal lung unit (TLU) is an agglomeration of alveoli that opens into the branching air spaces of respiratory bronchioles, alveolar ducts, and alveolar sacs and that these structures are covered by a continuous thin liquid layer bearing a monomolecular film of surfactants at the open gas-liquid interface. The inherent structural and functional instability given TLUs by a broad liquid surface layer of this nature has been mitigated by the discovery that the TLU surface is in fact an agglomeration of bubbles, a foam (the alveolar surface network) that fills the TLU space and forms ultrathin foam films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in parallel, throughout the TLU and between TLUs and the liquid surface of conducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting airways and pulmonary capillaries throughout the respiratory cycle. The experimental evidence, from discovery to the present, is addressed in this report. Lungs were examined in thorax by stereomicroscopy immediately from the in vivo state at volumes ranging from functional residual capacity to maximal volume (Vmax). Lungs were then excised; bubble topography of all anterior and anterolateral surfaces was reaffirmed and also confirmed for all posterior and posterolateral surfaces. The following additional criteria verify the ubiquitous presence of normal intraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individually by gentle microprobe pressure. 3) Adjoining bubbles move into the external medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift position in situ, while more distal bubbles remain stationary. 4) The position and movement of "large" bubbles identifies them as intraductal bubbles. 5) Transection of the lung reveals analogous bubble occurrence and history in central lung regions. 6) Bubbles become fixed in place and change shape when the lung is dried in air; the original shape and movement are restored when the lung is rewet. 7) All exteriorized bubbles are stable with lamellar (film) surface tension near zero. 8) Intact lungs prepared and processed by the new double-embedding technique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, transformations, and apparent function from birth through adulthood, as summarized in the following section. ANATOMY: Intraalveolar bubbles and bubble films (the unit structures of the alveolar surface network) have been found in all mammalian species examined to date, including lambs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pigs. Rabbits were used for the definitive studies. 1) A unit bubble occupies each alveolus and branching airway of the TLU; unit bubbles in clusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the TLUs. The appositions are bubble to bubble (near alveolar entrances, at pores of Kohn, and between ductal bubbles), bubble to epithelial cell surface, and bubble to surface liquid of conducting airways. They rapidly form stable Newtonian black foam films (approximately 7 nm thick) under hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-zero surface tension. At the same time, the foam film formations--abetted by the constant but small retractive force of tissue recoil--stabilize unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as liquid accumulates within the network (e.g. (ABSTRACT TRUNCATED)

Animals↗
PubMed1998

Case-control study of sun exposure and squamous cell carcinoma of the skin.

We conducted a case-control study of sun exposure and squamous cell carcinoma (SCC) of the skin within a population-based, longitudinal study of skin cancer. Cases had histopathologically confirmed SCC. Subjects were interviewed about their lifetime sun exposure, including exposure to the site of the SCC (sites for controls were assigned randomly). Analysis was restricted to 132 cases and 1,031 controls born in Australia and with no ancestors from southern Europe. The total site-specific exposure was strongly related to risk of SCC; the odds ratio increased to a maximum of 3.3 at 65,000 hr of exposure before falling slightly. Site-specific exposure during childhood and adolescence was more strongly associated with SCC than exposure during adulthood. An intermittent pattern of weekly sun exposure was not associated with SCC and the odds ratios for hours of exposure on vacation were close to unity. The number of blistering sunburns to the site was positively associated with SCC. Use of sunscreens and hats showed inconsistent effects. Sun exposure, especially during childhood and adolescence, increases the risk of SCC. The pattern of exposure appears to be unimportant, despite the association with sunburn, which may simply be an indicator of the skin's sensitivity to sunlight.

Adult↗
PubMed2000

Sunscreens and cutaneous malignant melanoma: an Italian case-control study.

The possible relation between use of sunscreens and the risk of cutaneous malignant melanoma (CMM) was investigated in a case-control study conducted in 27 Italian centres on 542 incident, histologically confirmed cases and 538 controls admitted for acute, other than neoplastic or dermatologic conditions. Compared with subjects reporting never sunscreen use, the multivariate odds ratios (OR), after allowance for age, sex, geographic area, education, skin, eye and hair colour, freckles, number of naevi, history of sunburns, tanning pattern and duration of sunny vacations, were 0.97 (95% confidence interval [CI] 0.69 to 1.35) for those reporting "sometimes" and 0.80 (95% CI 0.54 to 1.17) for those reporting "often " sunscreen use. With reference to type of product most frequently used, the ORs were 0.96 (95% CI 0.52 to 1.77) for minimal, 0.90 (95% CI 0.63 to 1.28) for moderate and 1.41 (95% CI 0.85 to 2. 35) for high sunburn protection factor. With reference to duration of use, the OR was 0.86 (95% CI 0.58 to 1.29) for use started since >/=20 years. None of the corresponding trends in risks were significant. The ORs for sunscreen use were similar across strata of major identified covariates and, if anything, tended to decline after multivariate analysis. The present findings confirm that sunscreen use, as currently adopted in Italy, is not appreciably related to subsequent CMM risk.

Adult↗
PubMed1998

Production of D-phenylglycine from racemic (D,L)-phenylglycine via isoelectrically-trapped penicillin G acylase.

Penicillin G acylase (PGA) is exploited for producing pure D-phenylglycine from a racemate mixture, via an acylation reaction onto a cosubstrate, the ester methyl-4-hydroxyphenyl acetate. The reaction, when carried in a batch, is severely hampered by the reverse process, by which the product, 4-hydroxyphenylacetyl-(L)phenyl glycine, upon consumption of L-phenylglycine, is converted by the enzyme back into free substrate and 4-hydroxyphenyl acetic acid via lysis of the amido bond. To prevent this noxious reaction, a multicompartment electrolyzer with isoelectric membranes (MIER) is used as enzyme reactor, operating in an electric field. PGA is trapped between pI 5.5 and pI 10.5 membranes, together with an amphoteric, isoelectric buffer (lysine). As the 4-hydroxyphenylacetyl-(L)phenyl glycine product is formed, it vacates the reaction chamber by electrophoretic transport and is collected close to the anode, in a chamber delimited by pI 2.5 and 4.0 membranes. The same fate occurs to the free acid 4-hydroxyphenyl acetic acid, formed upon spontaneous (and enzyme-driven) hydrolysis of the methyl ester in the reaction chamber. These combined processes leave behind, in the enzyme reaction chamber, the desired product, pure D-phenylglycine. The advantages of the MIER reactor over batch operations: the consumption of the L-form in the racemate is driven to completion and the enzyme is kept in a highly stable form, maintaining 100% activity after one day of operation, during which time the PGA enzyme, in the batch reactor, has already lost >75% catalytic activity.

Electrophoresis, Capillary↗
PubMed1999

Electrically immobilized enzyme reactors: bioconversion of a charged substrate. Hydrolysis Of penicillin G by penicillin G acylase.

The possibility of using the multicompartment immobilized enzyme reactor (MIER) in presence of a charged substrate is here explored. Penicillin G acylase is used to convert penicillin G (a free acid, with a pK of 2.6) into two charged products: phenyl acetic acid (PAA, with a pK of 4.2) and 6-aminopenicillanic acid (6-APA, a zwitterion with a pI of 3.6). The enzyme is trapped by an isoelectric mechanism in a chamber of the electrolyzer delimited by a pI 5.0 and a pI 9.0 amphoteric, isoelectric membranes. Under normal operating conditions (continuous substrate feeding in the presence of an electric field), only a low substrate conversion can be achieved, due to rapid electrophoretic transport of unreacted penicillin G out of the reaction chamber towards the anode. Excellent conversion rates (>96%) are obtained under a "doubly-discontinuous" operation mode: a time-lapse substrate feeding, accompanied by short times (4-8 min) of electric field interruption. The product of interest (6-APA, a precursor of semisynthetic penicillins), by virtue of its amphoteric nature, is trapped in a chamber delimited by a pI 3.5 membrane and a pI 5.5 membrane, adjacent to the reaction chamber on its anodic side. The other contaminant product (PAA) first accumulates in the same chamber and then progressively vacates it to collect in the anodic reservoir, leaving behind a pure 6-APA solution. In this operation mode, vanishing amounts of unreacted substrate (penicillin G) leave the reaction chamber to contaminate the adjacent, anodic chambers. A novel class of zwitterionic buffers is additionally reported, able to cover very thoroughly any pH value along the pH 3-10 interval: polymeric, zwitterionic buffers, synthesized with the principle of the Immobiline (acrylamido weak acids and bases) chemicals. Enhanced enzyme reactivity is found in this macromolecular buffers as compared to conventional ones.

Bioreactors↗
PubMed1998

Disproportionate loss of thin filaments in human soleus muscle after 17-day bed rest.

Previously we reported that, after 17-day bed rest unloading of 8 humans, soleus slow fibers atrophied and exhibited increased velocity of shortening without fast myosin expression. The present ultrastructural study examined fibers from the same muscle biopsies to determine whether decreased myofilament packing density accounted for the observed speeding. Quantitation was by computer-assisted morphometry of electron micrographs. Filament densities were normalized for sarcomere length, because density depends directly on length. Thick filament density was unchanged by bed rest. Thin filaments/microm2 decreased 16-23%. Glycogen filled the I band sites vacated by filaments. The percentage decrease in thin filaments (Y) correlated significantly (P < 0.05) with the percentage increase in velocity (X), (Y = 0.1X + 20%, R2 = 0.62). An interpretation is that fewer filaments increases thick to thin filament spacing and causes earlier cross-bridge detachment and faster cycling. Increased velocity helps maintain power (force x velocity) as atrophy lowers force. Atrophic muscles may be prone to sarcomere reloading damage because force/microm2 was near normal, and force per thin filament increased an estimated 30%.

Actin Cytoskeleton↗
PubMed1998

Intrauterine position, parenting, and nest-site attachment in male Mongolian gerbils.

We housed male Mongolian gerbils, their mates, and foster litters of standardized size and sex ratio in enclosures that provided cover in two locations. Males had been gestated in known intrauterine positions: either between two females (2F males) or between two males (2M males). From Days 1 to 20 postpartum, we examined the frequency with which both males and females were in contact with the pups they were rearing. We found that 2F males spent more time with pups than did 2M males both during entire observation periods and when females were away from the nest. Further, when pups were moved from the nest site. 2M males spent more time than did 2F males in the vacated nest site. We concluded that 2F male gerbils spent more time with pups than 2M males not because of a greater attachment of 2F than 2M males to places of concealment, their male, or their nest site. Rather, 2F males were more attracted to pups than were 2M males.

Analysis of Variance↗
PubMed1996

Electron microscopic analysis of lesion-induced changes in synaptic structure and immunogold labeling of neurotransmitters within the feline trigeminal nucleus.

This report uses lesion and postembedding immunogold protocols to examine the ultrastructural details of lesion-induced synaptic and neurotransmitter changes in the feline trigeminal nucleus. Electron microscopic (EM) analysis concentrated on lamina II (substantia gelatinosa) of the subnucleus pars caudalis (PC) which is one relay site or trigeminal fibers involved in nociception. Special attention was directed to analysis of reoccupation of synaptic sites vacated by primary afferent degeneration. Primary afferents are caused to degenerate by performing unilateral retrogasserian rhizotomy. After survival times of 1, 2, 6, and 7 days, sections of PC were processed for postembedding immunogold labeling with antibodies to the neurotransmitters gamma aminobutyric acid (GABA) and glutamate (Glu). The results show: (1) degenerating primary afferent terminals were easily identified in various stages of degeneration; (2) Glu immunoreactivity was observed in early forms of degenerated primary afferent terminals with clumped vesicles as well as in the highly distorted, electron dense terminals of later degeneration; and (3) some GABA immunoreactive terminals formed atypical synapses which exhibited both asymmetric (excitatory) and symmetric (inhibitory) synaptic densities. A possible model is presented of the progression of events following trigeminal nerve lesion which results in atypical synapse formation. Such altered synaptic relationships seen in PC following trigeminal rhizotomy may be related to hyperactivity that is seen in animals and to the atypical facial pain following nerve lesions in humans.

Animals↗
PubMed1989

Urinary excretion of chromium in chromeplaters after discontinued exposure.

In a previous study [Lindberg and Vesterberg, 1983a], excretion of chromium in urine (U-Cr) in chromeplaters was proposed for biological monitoring of ongoing exposure. Published reports were found about the decline of U-Cr after discontinued exposure in welders working in chromium-alloyed stainless steel, but not in chromeplaters. In this study, half-times (t1/2) were calculated for ten chromeplaters over a weekend, and for 23 chromeplaters over 31 days vacation. The results suggest that the excretion of chromium can be approximated to a two-compartment model. Estimated from the median values, an initial rapid phase with an assumed t1/2 of 2-3 days is followed by a phase with a t1/2 of approximately a month. Differences between the decline of U-Cr in chromeplaters and welders are discussed.

Chromates↗
PubMed1992

Hormone status in occupational toluene exposure.

Twenty toluene-exposed rotogravure printers, without signs of solvent-induced toxic encephalopathy, had lower median plasma levels of follicle stimulating hormone (FSH) (3.2 vs. 4.9 IU/L; p = .02) and luteinizing hormone (LH) (6.4 vs. 7.2 IU/L; p = .05) and also lower serum levels of free testosterone (7.8 vs. 86.8 pmol/L; p = .05), respectively, than 44 unexposed referents. The individual time-weighted toluene levels in air were 36 (median; range 8-111) ppm. The printers' median toluene levels in blood were 1.7 (1.0-6.6) mumol/l, and in subcutaneous adipose tissue 5.7 (2.5-21) mg/kg fat. There was a negative association between blood toluene and plasma levels of prolactin. In eight printers, the levels of FSH and LH increased during a 4 week vacation, while the levels of thyroid stimulating hormone, free triiodothyronine, and free thyroxine decreased during the same period. The results indicate a slight, reversible effect of toluene on the cortical level or on the hypothalamic-pituitary axis at exposures well below the permissible levels, possibly mediated through an effect on catecholamine neurotransmission.

Adipose Tissue↗
PubMed2000

Anti-stress effects of DHA.

DHA is abundant in the brain. Deficiency of DHA changes behavior in animals. The purpose of the present studies was to clarify the effect of DHA intake on hostility and plasma catecholamines. In study 1, forty-one students took either DHA-rich oil capsules containing 1.5-1.8 g DHA/d (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mon in a double blind fashion. They took a psychological test (P-F Study) at the start and end of the study. Study I started at the end of summer vacation and ended in the middle of mental stress of final exams. In the control group, hostility measured by P-F Study was significantly increased at the end of the study as compared with that measured at the start (+58%), whereas it was not significantly changed in the DHA group (-14%). In a similar double blind two-mon study (study 2), we measured plasma catecholamines and cortisol of students (3 females and 4 males for the DHA group and the same numbers for the control) at the start and end of the study. In study 2 the students were under a continuous stress of final exams that lasted for two mon throughout the whole study period. The plasma cortisol did not change in either group, but the norepinephrine concentration was significantly decreased in the DHA group (-31%), whereas it stayed at the same level in the control group. These effects of DHA intake may be applied to people under psychological stress.

Adult↗
PubMed2006

REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors.

We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are identified in silico by using a core peptide-bound protein structure as a design anchor. In the REPLACE application example, we present the effective replacement of two critical binding motifs in a lead protein-protein interaction inhibitor pentapeptide with more druglike phenyltriazole and diphenyl ether groups. These were identified through docking of fragment libraries into the volume of the cyclin-binding groove of CDK2/cyclin A vacated through truncation of the inhibitor peptide-binding determinants. Proof of concept for this strategy was obtained through the generation of potent peptide-small-molecule hybrids and by the confirmation of inhibitor-binding modes in X-ray crystal structures. This method therefore allows nonpeptide fragments to be identified without the requirement for a high-sensitivity binding assay and should be generally applicable in replacing amino acids as individual residues or groups in peptide inhibitors to generate pharmaceutically acceptable lead molecules.

Amino Acid Substitution↗
PubMed2002

Effects of age on the glial cells in the rhesus monkey optic nerve.

The optic nerve is a circumscribed white matter tract consisting of myelinated nerve fibers and neuroglial cells. Previous work has shown that during normal aging in the rhesus monkey, many optic nerves lose some of their nerve fibers, and in all old optic nerves there are both myelin abnormalities and degenerating nerve fibers. The present study assesses how the neuroglial cell population of the optic nerve is affected by age. To address this question, optic nerves from young (4-10 years) and old (27-33 years) rhesus monkeys were examined by using both light and electron microscopy. It was found that with age the astrocytes, oligodendrocytes, and microglia all develop characteristic cytoplasmic inclusions. The astrocytes hypertrophy and fill space vacated by degenerated nerve fibers, and they often develop abundant glial filaments in their processes. Oligodendrocytes and microglial cells both become more numerous with age, and microglial cells often become engorged with phagocytosed debris. Some of the debris can be recognized as degenerating myelin, and in general, the greater the loss of nerve fibers, the more active the microglial cells become.

Aging↗
PubMed1976

Neuroplasticity in the rearrangement of olfactory tract fibers after neonatal transection in hamsters.

Olfactory bulb efferent axons run caudally in the lateral olfactory tract (LOT) to end in a broad cortical field in the ventral forebrain. Principles governing the plastic rearrangement of this fiber population after early lesions were probed by cutting the tract in hamster pups and studying the distribution of surviving olfactory bulb projections in adulthood using silver and autoradiographic techniques. The spatial pattern of rearrangement proved to depend on the extent of the cut and also the age at which it was made. For example, after complete LOT section at seven days of age no bulb efferents appeared distal to the cut but the proximal projection increased in laminar thickness and spread laterally and medially beyond its normal cytoarchitectonic boundaries. This spread was less pronounced in animals with earlier or later lesions. After transection of only part of the LOT fibers at seven days of age the proximal input was similarly increased. Just distal to the transection, uncut fibers sprouted collaterals to fill the terminal sites vacated as a result of the lesion. In these cases, however, the farthest distal parts of the projection field lost their normal innervation. In a tentative interpretation of these data it is proposed that developing LOT fibers tend to conserve their total amount of axonal arbor. That is, when distal branches are pruned off surgically, the axon compensates by producing extra proximal branches. When an overabundance of proximal collaterals are produced in axons that have not been surgically pruned the growth of more distal axonal branches is stunted in compensation.

Animals↗