Improved synthesis of aluminium nanoparticles using ultrasound assisted approach and subsequent dispersion studies in di-octyl adipate.

The present work reports on an efficient and simple one pot synthetic approach for aluminium nanoflakes and nanoparticles based on the intensification using ultrasound and provides a comparison with the conventional approach to establish the cutting edge process benefits. In situ passivation of aluminium particles with oleic acid was used as the method of synthesis in both the conventional and ultrasound assisted approaches. The aluminium nanoflakes prepared using the ultrasound assisted approach were subsequently dispersed in di-octyl adipate (DOA) and it was demonstrated that a stable dispersion of aluminium nanoflakes into di-octyl adipate (DOA) is achieved. The morphology of the synthesized material was established using the transmission electron microscopy (TEM) analysis and energy dispersive X-ray analysis (EDX) and the obtained results confirmed the metal state and nano size range of the obtained aluminium nanoflakes and particles. The stability of the aluminium nanoflakes obtained using ultrasound assisted approach and nanoparticles using conventional approach were characterized using the zeta potential analysis and the obtained values were in the range of -50 to +50mV and -100 to +30mV respectively. The obtained samples from both the approaches were also characterized using X-ray diffraction (XRD) and particle size analysis (PSA) to establish the crystallite size and particle distribution. It was observed that the particle size of the aluminium nanoflakes obtained using ultrasound assisted approach was in the range of 7-11nm whereas the size of aluminium nanoparticles obtained using conventional approach was much higher in the range of 1000-3000nm. Overall it was demonstrated that the aluminium nanoflakes obtained using the ultrasound assisted approach showed excellent morphological characteristics and dispersion stability in DOA showing promise for the high energy applications.

Effects of simultaneous repeated exposure at high levels of arsenic and malathion on hepatic drug-biotransforming enzymes in broiler chickens.

Groundwater contamination with arsenic is a major global health concern. The organophosphorus insecticide malathion has gained significance as an environmental pollutant due to its widespread use in agriculture, grain storage, ectoparasite control and public health management. The deleterious effects produced by arsenic or malathion alone are documented, but very little is known about the consequences of their coexposure. The aim of the current study was to examine the effects of repeated simultaneous exposure to arsenic and malathion on drug-biotransforming enzymes in the liver of broiler chickens. One-month-old broiler chickens were exposed daily to arsenic (50 ppm)-supplemented drinking water, malathion (500 ppm)-mixed diet or in a similar fashion coexposed to these agents for 28 days. At the term, changes in body weight, organ weights, and levels of hepatic cytochrome P450 (CYP), cytochrome b(5), microsomal and cytosolic proteins; aminopyrine N-demethylase (ANDM), aniline P-hydroxylase (APH), glutathione S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) were assessed. Arsenic, malathion or their coexposure decreased the body weight gain and liver weight. Brain weight (relative) was increased with arsenic or malathion, but not with the coexposure. Treatment with arsenic decreased the CYP and cytochrome b(5) contents by 39 and 36%, than with malathion by 54 and 22% and the coexposure by 45 and 28%, respectively. The ANDM activity was decreased with arsenic (44%), malathion (23%) and the coexposure (32%). Arsenic (23%) and the coexposure (37%), but not malathion (14%), reduced the APH activity. The activities of hepatic microsomal and cytosolic GST were increased with all the three treatments [Arsenic (microsomal: 88% cytosolic: 113%), malathion (microsomal: 137%, cytosolic: 94%) and coexposure (microsomal: 140%, cytosolic: 148%)]. These treatments did not significantly affect the hepatic UGT activity, but reduced the hepatic microsomal (arsenic: 28%, malathion: 34% and coexposure: 43%) and cytosolic (17-19%) protein contents. The effects of coexposure on the activities of various phase I and phase II drug-biotransforming enzymes were almost similar to that of arsenic or malathion. This study provides evidence that repeated coexposure to arsenic and malathion may influence the extent of drug metabolism in chickens.

Interactive alterations of arsenic and malathion in the disposition kinetics of pefloxacin.

Assessment of deleterious effects produced by concurrent exposure to commonly encountered chemicals is of great concern to find out toxicological consequences arising as a result of their interactions and for a more comprehensive management of chemical-induced untoward effects. The naturally occurring heavy metal arsenic is present in food and water. Malathion is one of the most widely used pesticides in agriculture and public health practices worldwide. Humans, animals, and birds are exposed to these chemicals through environmental processes. Since arsenic and malathion are shown to exert an inhibitory effect on cytochrome P450 activities, their continuous exposure may alter the disposition kinetics of drugs that are predominantly metabolized hepatically. The current study was undertaken to evaluate the impact of subchronic exposure of arsenic, malathion, and their combination on the disposition kinetics of widely used fluoroquinolone antimicrobial pefloxacin in chickens. Broiler chickens were exposed to either arsenic (50 ppm), malathion (500 ppm), or arsenic (50 ppm) plus malathion (500 ppm). Arsenic and malathion were given in drinking water and feed, respectively. Following 28 days of exposure, all birds received a single oral dose of pefloxacin (10 mg/kg) and the plasma concentrations and the disposition kinetic parameters of the drug were determined. In the birds not exposed to arsenic and/or malathion, the elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (C(max)), mean residence time (MRT), and bioavailability of pefloxacin were 8.46 +/- 0.24 h, 39.06 +/- 1.13 microg.h.ml(-1), 2.69 +/- 0.19 microg.ml(-1), 12.29 +/- 0.48 h, and 60.52 +/- 1.74%, respectively. Exposure to arsenic was associated with a significant increase in C(max) (4.28 +/- 0.45 microg.ml(-1)) and a nonsignificant increase in the values of AUC (48.96 +/- 2.55 microg.h.ml(-1)) and bioavailability (74.55 +/- 3.8 %) of pefloxacin. The values of AUC (51.62 +/- 4.76 microg.h.ml(-1)), t(1/2beta) (12.57 +/- 1.26 h), MRT (19.94 +/- 1.99 h), and bioavailability (78.59 +/- 7.25 %) of pefloxacin were significantly increased in malathion-exposed birds. Concomitant exposure to arsenic and malathion did not affect the disposition kinetic variables of pefloxacin. The study shows that subchronic malathion exposure significantly alters the elimination kinetics of pefloxacin. Following concurrent exposure, arsenic nullifies the malathion-induced changes in disposition kinetics of pefloxacin by possibly diminishing the cytochrome P450-catalyzed bioactivation of malathion.

Effects of subchronic malathion exposure on the pharmacokinetic disposition of pefloxacin.

Malathion is one of the most extensively used organophosphorus pesticides applied in agriculture, mosquito eradication and in the control of animal ectoparasites and human body lice. The widespread use of malathion has raised concern over its potential to cause untoward health effects in humans, animals and birds. Malathion inhibits cytochrome P450 monooxygenases and has the potential to alter pharmacokinetic profiles of therapeutic agents that are metabolized in the liver. The present study was undertaken to evaluate the impact of subchronic exposure of malathion on the pharmacokinetic disposition of pefloxacin. Chickens were given either normal diet or malathion through food at a concentration of 1000ppm for 28 days. Subsequently, pefloxacin was administered either intravenously or orally (control) to birds fed normal diet and orally to malathion-exposed chickens at a dosage of 10mgkg(-1) body weight. Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Plasma was separated and analyzed for pefloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data were analyzed by non-compartmental techniques. Following intravenous administration of pefloxacin, elimination half-life (t(1/2ß)), area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were 8.2±0.7h, 66±9µghml(-1) and 10.5±1.1h, respectively, and when the drug was administered orally, the respective values of pharmacokinetic parameters were 8.2±0.4h, 31±3.1µghml(-1) and 11.7±0.6h. Malathion exposure significantly increased maximum plasma drug concentration, t(1/2ß), AUC and MRT of pefloxacin to 54, 22, 117 and 37% of control, respectively. These findings provide evidence that subchronic malathion exposure markedly influences the elimination kinetics of pefloxacin which may be due to malathion-mediated inhibition of metabolism of pefloxacin.

Immunological characterization of T-type voltage-dependent calcium channel CaV3.1 (alpha 1G) and CaV3.3 (alpha 1I) isoforms reveal differences in their localization, expression, and neural development.

Low voltage-activated calcium channels (LVAs; "T-type") modulate normal neuronal electrophysiological properties such as neuronal pacemaker activity and rebound burst firing, and may be important anti-epileptic targets. Proteomic analyses of available alpha 1G/Ca(V)3.1 and alpha 1I/Ca(V)3.3 sequences suggest numerous potential isoforms, with specific alpha 1G/Ca(V)3.1 or alpha 1I/Ca(V)3.3 domains postulated to be conserved among isoforms of each T-type channel subtype. This information was used to generate affinity-purified anti-peptide antibodies against sequences unique to alpha 1G/Ca(V)3.1 or alpha 1I/Ca(V)3.3, and these antibodies were used to compare and contrast alpha 1G/Ca(V)3.1 and alpha 1I/Ca(V)3.3 protein expression by western blotting and immunohistochemistry. Each antibody reacted with appropriately sized recombinant protein in HEK-293 cells. Regional and developmental differences in alpha 1G/Ca(V)3.1 and alpha 1I/Ca(V)3.3 protein expression were observed when the antibodies were used to probe regional brain dissections prepared from perinatal mice and adult rodents and humans. Mouse forebrain alpha 1G/Ca(V)3.1 (approximately 240 kDa) was smaller than cerebellar (approximately 260 kDa) alpha 1G/Ca(V)3.1, and expression of both proteins increased during perinatal development. In contrast, mouse midbrain and diencephalic tissues evidenced an alpha 1I/Ca(V)3.3 immunoreactive doublet (approximately 230 kDa and approximately 190 kDa), whereas other brain regions only expressed the small alpha 1I/Ca(V)3.3 isoform. A unique large alpha 1I/Ca(V)3.3 isoform (approximately 260 kDa) was expressed at birth and eventually decreased, concomitant with the appearance and gradual increase of the small alpha 1I/Ca(V)3.3 isoform. Immunohistochemistry supported the conclusion that LVAs are expressed in a regional manner, as cerebellum strongly expressed alpha 1G/Ca(V)3.1, and olfactory bulb and midbrain contained robust alpha 1I/Ca(V)3.3 immunoreactivity. Finally, strong alpha 1I/Ca(V)3.3, but not alpha 1G/Ca(V)3.1, immunoreactivity was observed in brain and spinal cord by embryonic day 14 in situ. Taken together, these data provide an anatomical and biochemical basis for interpreting LVA heterogeneity and offer evidence of developmental regulation of LVA isoform expression.

Skilled finger movement exercise improves hand function.

BACKGROUND: Aging is accompanied by a marked decline in muscle strength and ability to maintain steady submaximal force. Studies have shown that exercise programs can improve age-related regression of hand function in elderly individuals. The purpose of this study was to train elderly subjects to perform skilled finger movements and to evaluate the changes in hand function involving skillful use of finger pinch. METHODS: Grip strength, maximum pinch force (MPF), steadiness of pinch force at 5%, 10%, and 20% MPF, M wave, and Hoffman (H) reflex were measured. Fourteen elderly subjects were trained with skilled finger movements, and their performance involving finger pinch was measured. RESULTS: Compared with untrained elderly subjects, the trained older adults significantly (p <.05) improved their ability to control submaximal pinch force, to maintain a steady hand posture, and to relocate a small object quickly with finger grip. The amplitude of H reflex increased significantly for the trained group. CONCLUSIONS: Skilled finger movement training improves the ability to control submaximal pinch force, hand steadiness, and manual speed in elderly subjects; these improvements may be due to training-induced adaptations in the central and peripheral nervous systems.

Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit.

Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3-5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of NBS cells to survive gamma irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients.

Steroidogenic acute regulatory protein expression is dependent upon post-translational effects of cAMP-dependent protein kinase A.

Tropic hormones acutely stimulate adrenal and gonadal steroidogenesis by activation of the cAMP-dependent protein kinase A (PKA) signaling pathway and subsequent induction of Steroidogenic Acute Regulatory (StAR) protein (StAR) expression. We present a comparative study of StAR regulation in mouse adrenocortical Y1 and the derived PKA mutant Kin-8 cell lines to evaluate the PKA requirement for StAR expression. A parallel increase in StAR steady-state mRNA and protein was observed in Y1 cells. StAR mRNA was induced in 8-Br-cAMP-treated Kin-8 cells with maximal expression levels approx. 50% of that observed in Y1 cells. However, a corresponding increase in StAR protein, as detected by Western analysis, was absent in the Kin-8 cells. A similar distribution of StAR mRNA in active polysome fractions was observed for both 8-Br-cAMP-treated Y1 and Kin-8 cells, as well as a 2-fold increase in incorporation of [35S]methionine into StAR, which indicated translation was not blocked in Kin-8 cells. Together these data indicate that PKA functions at the post-translational level to regulate StAR expression and we propose that phosphorylation of StAR by PKA contributes to protein stability

Effects of aging on hand function.

OBJECTIVES: The purpose of this study was to quantify age-induced changes in handgrip and finger-pinch strength, ability to maintain a steady submaximal finger pinch force and pinch posture, speed in relocating small objects with finger grip, and ability to discriminate two identical mechanical stimuli applied to the finger tip. DESIGN: A cross-sectional study. SETTINGS: Greater Cleveland area of Ohio. PARTICIPANTS: Healthy, independent, young (n = 27, range 20-35 years) and older (n = 28, range 65-79 years) subjects. MEASUREMENTS: Handgrip strength, maximum pinch force (MPF), ability to maintain a steady pinch force at three relative force levels (5%, 10%, and 20% MPF) and three absolute force levels (2.5 Newtons (N), 4 N, and 8 N), ability to maintain a precision pinch posture, speed in relocating pegs from a nearby location onto the pegboard, and the shortest distance for discriminating two stimuli were measured in both young and older groups. RESULTS: Compared with young subjects, the older group's handgrip force was 30% weaker (P < .001), MPF was 26% lower (P < .05), and ability to maintain steady submaximal pinch force and a precision pinch posture was significantly less (P < .05). The time taken to relocate the pegs and the distance needed to discriminate two identical stimuli increased significantly with age (P < .01). The decrease in the ability to maintain steady submaximal pinch force was more pronounced in women than men. CONCLUSION: Aging has a degenerative effect on hand function, including declines in hand and finger strength and ability to control submaximal pinch force and maintain a steady precision pinch posture, manual speed, and hand sensation.

Relationship between motor activity-related cortical potential and voluntary muscle activation.

The purpose of this study was to investigate the relationship between EEG-derived motor activity-related cortical potential (MRCP) and voluntary muscle activation. Eight healthy volunteers participated in two experimental sessions. In one session, subjects performed isometric elbow-flexion contractions at four intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In another session, a given elbow-flexion force (35% MVC) was generated at three different rates (slow, intermediate, and fast). Thirty to 40 contractions were performed at each force level or rate. EEG signals were recorded from the scalp overlying the supplementary motor area (SMA) and contralateral sensorimotor cortex, and EMG signals were recorded from the skin surface overlying the belly of the biceps brachii and brachioradialis muscles during all contractions. In each trial, the force was used as the triggering signal for MRCP averaging. MRCP amplitude was measured from the beginning to the peak of the negative slope. The magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA) was highly correlated with elbow-flexion force, rate of rising of force, and muscle EMG signals. These results suggest that MRCP represents cortical motor commands that scale the level of muscle activation.

ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.

Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to gamma-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by gamma-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after gamma-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.

Brain activation during human finger extension and flexion movements.

Corticospinal projections to the motor neuron pool of upper-limb extensor muscles have been reported to differ from those of the flexor muscles in humans and other primates. The influence of this difference on the central nervous system control for extension and flexion movements is unknown. Cortical activation during thumb extension and flexion movements of eight human volunteers was measured using functional magnetic resonance imaging (fMRI), which detects signal changes caused by an alteration in the local blood oxygenation level. Although the relative activity of the extensor and flexor muscles of the thumb was similar, the brain volume activated during extension was substantially larger than that during flexion. These fMRI results were confirmed by measurements of EEG-derived movement-related cortical potential. Higher brain activity during thumb extension movement may be a result of differential corticospinal, and possibly other pathway projections to the motoneuron pools of extensor and flexor muscles of upper the extremities.

Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells.

The pro-apoptotic protein, Bax, has been reported to translocate from cytosol to mitochondria following exposure of cells to apoptotic stresses including cytokine withdrawal and treatment with glucocorticoids and cytotoxic drugs. These observations, coupled with reports showing that Bax causes the release of mitochondrial cytochrome c, implicate Bax as a central mediator of the apoptotic process. In this report we demonstrate by subcellular fractionation a significant shift in Bax localization from cytosol to cellular membranes in two human tumor cell lines exposed to staurosporine or etoposide. Immunofluorescence studies confirmed that Bax specifically relocalized to the mitochondria. This redistribution of Bax occurred in concert with, or just prior to, proteolytic processing of procaspase-3, activation of DEVD-specific cleavage activity and degradation of poly(ADP-ribose) polymerase. However, Bax membrane translocation was independent of caspase activity as determined using the broad-range caspase inhibitor z-VAD-fmk. High level overexpression of the anti-apoptotic protein Bcl-2 prevented Bax redistribution to the mitochondria, caspase activation and apoptosis following exposure to staurosporine or etoposide. These data confirm the role of Bax in mitochondrial cytochrome c release, and indicate that prevention of Bax translocation to the mitochondrial membrane represents a novel mechanism by which Bcl-2 inhibits drug-induced apoptosis.

Evidence of inability to fully activate human limb muscle.

The purpose of this study was to determine whether muscle activation level estimated by twitch interpolation technique was different when an electrical stimulus was applied during a dynamic force (DF; force rising) task from that when the stimulus was applied during a static force (SF; constant force) task. Fourteen subjects performed voluntary SF and DF contractions involving isometric elbow flexion at seven voluntary force levels. At each level, the electrical stimulation was applied to the surface of the biceps brachii muscle when the force was steady (SF task) and when the force was rising (DF task). The voluntary activation level of the biceps brachii muscle during the SF maximal voluntary contraction (MVC) was 98.5% and that during the DF MVC task was significantly lower (94.5%; P < 0.05). The motoneurons and/or muscle fibers may become more excitable during the DF task so that the same stimulus can recruit those that are otherwise less excitable during the SF task.

Post-translational regulation of steroidogenic acute regulatory protein by cAMP-dependent protein kinase A.

Adrenal steroid production is stimulated by adrenocorticotropin hormone activation of the cAMP-dependent protein kinase A (PKA) signaling pathway and subsequent induction of Steroidogenic Acute Regulatory (StAR) protein expression. Herein we have compared StAR mRNA and protein levels in 8-Br-cAMP-treated mouse adrenocortical Y1 and the derived PKA mutant Kin-8 cell lines to evaluate the PKA requirement in StAR expression. StAR mRNA was induced by 8-Br-cAMP-treatment of both Y1 and Kin-8 cells with maximal expression levels in Kin-8 cells approximately 50% of that observed in Y1 cells. StAR protein levels, as detected by Western analysis, were concomitantly increased in Y1 cells but were not detected in the Kin-8 cells. StAR mRNA colocalized with the active polysome fractions in both 8-Br-cAMP-treated Y1 and Kin-8 cells, indicating translation was not blocked in Kin-8 cells. Consistent with this data, a 2-fold increase in incorporation of [35S]methionine into StAR was also observed after 8-Br-cAMP treatment of both cell lines. Since StAR protein levels were not sufficient to detect by Western analysis, these data indicate that PKA functions at the post-translational level to regulate StAR expression and we propose that phosphorylation of StAR by PKA contributes to protein stability.

Bcl-2 inhibits early apoptotic events and reveals post-mitotic multinucleation without affecting cell cycle arrest in human epithelial tumor cells exposed to etoposide.

UNLABELLED: Defective apoptotic mechanisms are considered to play a role in both the development of malignancy and resistance to chemotherapeutic drugs. The Bcl-2 family of proteins regulate the cellular commitment to survive or die when challenged with various apoptotic stimuli. PURPOSE: The purpose of this study was to identify the point at which Bcl-2 interrupts the apoptotic cascade initiated following exposure of human tumor cells to etoposide. METHODS: A stable Bcl-2-expressing HeLa-transfected clonal cell line, along with its control-vector-transfected counterpart, were utilized in this study. Following etoposide exposure, cells were examined for cell cycle arrest, formation of hyperdiploid cells, apoptotic DNA degradation, loss of plasma membrane integrity, levels of expression of members of the Bcl-2 protein family, caspase activation, degradation of poly(ADP-ribose) polymerase and movement of Bax from cytosol to cellular membrane fractions. RESULTS: Caspase activation, poly(ADP-ribose) polymerase degradation and Bax membrane insertion were initiated rapidly following etoposide removal, concomitantly with cell cycle arrest. Whereas Bcl-2 had no effect on etoposide-induced cell arrest, it interrupted all aspects of apoptosis, including activation of caspases, poly(ADP-ribose) polymerase degradation, DNA fragmentation and loss of plasma membrane integrity. Surprisingly, Bcl-2 also blocked Bax membrane insertion. In addition, Bcl-2 also prevented the increase in cellular levels of Bak, Bax and Bcl-xL, along with degradation of actin and Bax. However, inhibition of etoposide-induced apoptosis by Bcl-2 resulted in the accumulation of giant, multinucleated cells that eventually lost the ability to exclude trypan blue without apoptotic morphology or DNA degradation. CONCLUSIONS: These results indicate that biochemical apoptotic processes are initiated concomitant with etoposide-induced cell cycle arrest and are interrupted by Bcl-2 overexpression. However, the aberrant mitotic events induced by etoposide are sufficient to kill these cells even in the absence of apoptosis.

Older adults exhibit a reduced ability to fully activate their biceps brachii muscle.

BACKGROUND: Voluntary muscle strength declines significantly in older adults. One contributing factor to the strength loss is muscle atrophy developed in old age. Whether the ability to maximally activate the muscle decreases with age, however, is unknown. This study was intended to determine if the central nervous system command to maximally activate the biceps brachii muscle deteriorates with age. METHODS: Electrical stimulation pulses were applied to the skin overlying the biceps brachii muscle during maximal voluntary elbow-flexion contractions. The magnitude of force evoked on the maximal voluntary force was measured to determine the activation level (AL) of the muscle. RESULTS: The AL was 94% for the elderly group and 97% for the young group (100% AL indicates complete activation). The AL for both the elderly and young groups was significantly (p<.05) lower than 100%. The AL of the elderly group was significantly (p<.05) lower than that of the young group. CONCLUSIONS: The loss of voluntary strength in older adults is a mixed result of muscle atrophy and a reduced ability to fully activate muscle.

Hormonal effects on hamster lacrimal gland female-specific major 20 kDa secretory protein and its immunological similarity with submandibular gland major male-specific proteins.

Hormonal regulation of a major 20 kDa protein of hamster exorbital lacrimal gland (LG) was studied by SDS-PAGE profile analysis and the purified protein's antisera was used to screen tissues of hamster and other species for crossreacting proteins. This protein was seen in female LG but not in males and late-pregnant or hCG-treated females. Low estrogen state in females after gonadectomy, prolonged light-deprivation, prolonged starvation or lactation increased its level several folds to approximately 20% of LG soluble proteins and similar levels were induced in males after gonadectomy (low androgen state). However, light-deprivation or melatonin treatment-induced low androgen state in males had no effect. In gonadectomized hamsters, this LG protein was obliterated on treatment with androgens, estrogens or thyroid hormones. Only estrogen inhibition of LG 20 kDa was prevented by simultaneous tamoxifen administration. Simultaneous treatment of gonadectomized hamsters with gonadotrophins and estrogen/androgen did not prevent the LG 20 kDa protein's inhibition. Relative potencies of estrogens (3.6 microg daily dose) were: estradiol-17beta approximately diethylstilbestrol > estrone > estradiol-17alpha, while estriol and chlorotrianisene had no effect. Dexamethasone, progesterone, prolactin, hypothyroid state or adrenalectomy had no effect on LG 20 kDa expression. Western blot studies confirmed the marked repression of LG 20 kDa by estrogen androgen and thyroid hormone and detected the protein in tears of females and gonadectomized hamsters but not in males. Interestingly, among other tissues tested, crossreaction was only seen with the estrogen-repressed 24 and 20.5 kDa major male-specific secretory proteins of hamster submandibular glands (SMG) which were previously reported by us. This strongly indicated that the LG and SMG proteins are products of the same or closely related genes. A possible role for these hamster sex-specific LG and SMG major secretory proteins in olfactory communication is suggested.