ADM
Pro-adrenomedullin precursor [Contains: Adrenomedullin (AM); Proadrenomedullin N-20 terminal peptide (ProAM N-terminal 20 peptide) (PAMP) (ProAM-N20)] [AM]
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Decomposition-based quantitative electromyography (DQEMG) is one method of measuring neuromuscular physiology in human muscles. The objective of the current study is to compare the neuromuscular physiology of a typical aging population in the intrinsic hand muscles. Measurements of DQEMG were detected with a standard concentric needle and surface EMG from the intrinsic hand muscles. DQEMG was obtained from the first dorsal interosseous (FDI), the abductor digiti minimi (ADM) and fourth dorsal interosseous (4DI). Multivariate analysis of variance (MANOVA) were performed for the surface and intramuscular EMG measures to identify age differences in motor unit properties. Large differences were observed between the age groups for the canonical intramuscular and surface EMG variables. Older adults demonstrated a large decrease in motor unit number estimation in the ADM and FDI. Likewise, medium to large decreases in motor unit stability were observed in the FDI, ADM and 4DI. With aging, there are decreases in motor unit number estimation and stability in the intrinsic hand muscles. Using a multivariate approach allows for age-related differences and the relationship between the variables to be further elucidated. Multivariate analysis of DQEMG may be useful for identifying patterns of change in neuromuscular physiology with age-related changes to hand musculature. This may potentially lead to future prognostic biomarkers of age-related changes to hand muscles.
Keywords
- Aging
- Decomposition-based quantitative electromyography (DQEMG)
- Hand muscle
- Jiggle
- Motor unit potential (MUP)
- Multivariate
Using a cross sectional design, we aimed to identify the effect of aging on sensorimotor function and cortical motor representations of two intrinsic hand muscles, as well as the course and timing of those changes. Furthermore, the link between cortical motor representations, sensorimotor function, and intracortical inhibition and facilitation was investigated. Seventy-seven participants over the full adult lifespan were enrolled. For the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscle, cortical motor representations, GABA -mediated short-interval intracortical inhibition (SICI), and glutamate-mediated intracortical facilitation (ICF) were assessed using transcranial magnetic stimulation over the dominant primary motor cortex. Additionally, participants' dexterity and force were measured. Linear, polynomial, and piecewise linear regression analyses were conducted to identify the course and timing of age-related differences. Our results demonstrated variation in sensorimotor function over the lifespan, with a marked decline starting around the mid-thirties. Furthermore, an age-related reduction in cortical motor representation volume and maximal MEP of the FDI, but not for ADM, was observed, occurring mainly until the mid-forties. Area of the cortical motor representation did not change with advancing age. Furthermore, cortical motor representations, sensorimotor function, and measures of intracortical inhibition and facilitation were not interrelated.
Keywords
- Transcranial Magnetic Stimulation (TMS)
- aging
- cortical motor representation
- intracortical inhibition/facilitation
- sensorimotor performance
Chronological age is considered one of the major risk factors for cardiovascular disease and mortality. The study aimed to evaluate the transcriptional levels of the natriuretic peptides (NP), endothelin (ET)-1, adrenomedullin (ADM), their receptors and long non-coding (Lnc) RNA MIAT, MALAT-1, CARMEN and XIST in rat cardiac tissue as cardiovascular biomarkers of aging. Three groups of male Wistar rats were studied: A (n = 6; young), B (n = 13; adult), C (n = 10; old). Total RNA was extracted from left ventricle and analyzed by Real-Time PCR. Echocardiographic and histological analyses were performed. A significant increase of Atrial NP (ANP) and Brain NP (BNP) mRNA was observed in C while C-type NP (CNP) remained in a steady-state in B and C; ET-1 mRNA increased significantly as a function of age. Any difference was observed for NP receptors. ETA expression was statistically lower in B than A while ETB were similar in all the three groups. The ADM showed an opposite trend to that of the other peptides decreasing significantly as a function of age and presenting a counter-regulation of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP)-2. LncRNA transcripts decreased significantly as a function of age except for XIST. ADM and LncRNA trend suggest that the animals are subjected to "successful aging" as also confirmed by histological analysis. Applying a multivariate logistic regression analysis, only LnANP (p = 0.003) and LnADM (p = 0.023) resulted significantly associated with aging identifying them, for the first time, as independent markers of aging. The study underlining the importance of a multi-label biomolecular approach in the evaluation of aging.
Keywords
- ADM system
- Aging
- Biomarkers
- ET-1system
- LncRNA
- NP system
The endosymbiotic bacterium Wolbachia spreads rapidly through populations of Aedes aegypti mosquitoes, and strongly inhibits infection with key human pathogens including the dengue and Zika viruses. Mosquito control programs aimed at limiting transmission of these viruses are ongoing in multiple countries, yet there is a dearth of mass rearing infrastructure specific to Wolbachia-infected mosquitoes. One example is the lack of a blood meal substitute, which accounts for the Wolbachia-specific physiological changes in infected mosquitoes, that allows the bacterium to spread, and block viral infections. To that end, we have developed a blood meal substitute specifically for mosquitoes infected with the wMel Wolbachia strain. This diet, ADM, contains milk protein, and infant formula, dissolved in a mixture of bovine red blood cells and Aedes physiological saline, with ATP as a phagostimulant. Feeding with ADM leads to high levels of viable egg production, but also does not affect key Wolbachia parameters including, bacterial density, cytoplasmic incompatibility, or resistance to infection with Zika virus. ADM represents an effective substitute for human blood, which could potentially be used for the mass rearing of wMel-infected A. aegypti, and could easily be optimized in the future to improve performance.
MeSH Terms
- Aedes
- Animals
- Cattle
- Cytoplasm
- Diet
- Erythrocytes
- Feeding Behavior
- Female
- Fertility
- Humans
- Longevity
- Male
- Wolbachia
- Zika Virus
- Zika Virus Infection
This study examined age group differences in the rates of depression diagnosis and treatment using a national probability sample. Using data from the 2012 National Ambulatory Medical Care Survey (n=62,723 visits by patients aged 18 years), we used bivariate and multivariable binary logistic regression analyses to test age group differences in antidepressant medication (ADM) and psychotherapy prescribed/ordered or provided at visits during which depression was diagnosed. Visits by older adults were less likely to result in a depression diagnosis than visits by younger individuals: 2.46% and 1.80% in the 65-74 and 75 age groups, compared to 4.06%, 4.24% and 4.12% in the 18-29, 30-49 and 50-64 age groups, respectively. Of all visits involving diagnosed depression, 65.88% included prescribing/ordering or providing ADM and 19.01% included psychotherapy ordering or providing, without significant age group difference. Prescribing/ordering or providing ADM occurs frequently during visits to physicians regardless of specialty, while psychotherapy was ordered or provided mostly during visits to psychiatrists. During ambulatory care visits in which depression was diagnosed, older adults were as likely as younger adults to be prescribed/provided treatment; however, in more than 30% of visits by depressed older adults neither ADM nor psychotherapy was prescribed.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Ambulatory Care
- Antidepressive Agents
- Delivery of Health Care
- Depression
- Depressive Disorder
- Female
- Health Care Surveys
- Humans
- Male
- Middle Aged
- Psychotherapy
- Young Adult
Keywords
- Aging
- Antidepressants
- Depression
- Mental health
- Psychotherapy
Trans-differentiation of pancreatic acinar cells into ductal-like lesions, a process defined as acinar-to-ductal metaplasia (ADM), is observed in the course of organ regeneration following pancreatitis. In addition, ADM is found in association with pre-malignant PanIN lesions and correlates with an increased risk of pancreatic adenocarcinoma (PDAC). Human PDAC samples show down-regulation of p21(WAF1) (/Cip1) , a key regulator of cell cycle and cell differentiation. Here we investigated whether p21 down-regulation is implicated in controlling the early events of acinar cell trans-differentiation and ADM formation. p21-mediated regulation of ADM formation and regression was analysed in vivo during the course of cerulein-induced pancreatitis, using wild-type (WT) and p21-deficient (p21(-/-) ) mice. Biochemical and immunohistochemical methods were used to evaluate disease progression over 2 weeks of the disease and during a recovery phase. We found that p21 was strongly up-regulated in WT acinar cells during pancreatitis, while it was absent in ADM areas, suggesting that p21 down-regulation is associated with ADM formation. In support of this hypothesis, p21(-/-) mice showed a significant increase in number and size of metaplasia. In addition, p21 over-expression in acinar cells reduced ADM formation in vitro, suggesting that the protein regulates the metaplastic transition in a cell-autonomous manner. p21(-/-) mice displayed increased expression and relocalization of β-catenin both during pancreatitis and in the subsequent recovery phase. Finally, loss of p21 was accompanied by increased DNA damage and development of senescence. Our findings are consistent with a gate-keeper role of p21 in acinar cells to limit senescence activation and ADM formation during pancreatic regeneration.
MeSH Terms
- Animals
- Cell Cycle
- Cell Differentiation
- Cell Proliferation
- Cellular Senescence
- Ceruletide
- Cyclin-Dependent Kinase Inhibitor p21
- Disease Models, Animal
- Down-Regulation
- In Vitro Techniques
- Metaplasia
- Mice
- Mice, Knockout
- Pancreas
- Pancreatitis
- Regeneration
- beta Catenin
Keywords
- ADM
- p21
- pancreatitis
- senescence
- β-catenin
To better understand the physiological mechanisms responsible for the differential motor cortex functioning in aging, we used transcranial magnetic stimulation to investigate interhemispheric interactions and cortical representation of hand muscles in the early phase of physiological aging, correlating these data with participants' motor abilities. Right-handed healthy subjects were divided into a younger group (n = 15, mean age 25.4 ± 1.9 years old) and an older group (n = 16, mean age 61.1 ± 5.1 years old). Activity of the bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM) was recorded. Ipsilateral silent period (ISP) was measured in both APBs. Cortical maps of APB and ADM were measured bilaterally. Mirror movements (MM) were recorded during thumb abductions. Motor abilities were tested using Nine Hole Peg Test, finger tapping, and grip strength. ISP was reduced in the older group on both sides, in terms of duration (p = 0.025), onset (p = 0.029), and area (p = 0.008). Resting motor threshold did not differ between groups. APB and ADM maps were symmetrical in the younger group, but were reduced on the right compared to the left hemisphere in the older group (p = 0.008). The APB map of the right hemisphere was reduced in the older group compared to the younger (p = 0.021). Older subjects showed higher frequency of MM and worse motor abilities (p < 0.001). The reduction of right ISP area correlated significantly with the worsening of motor performances. Our results showed decreased interhemispheric interactions in the early processes of physiological aging and decreased cortical muscles representation over the non-dominant hemisphere. The decreased ISP and increased frequency of MM suggest a reduction of transcallosal inhibition. These data demonstrate that early processes of normal aging are marked by a dissociation of motor cortices, characterized, at least, by a decline of the non-dominant hemisphere, reinforcing the hypothesis of the right hemi-aging model.
Keywords
- ipsilateral silent period
- motor performances
- muscle cortical maps
- physiological aging
- transcranial magnetic stimulation
Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED. 302 non-surgical patients aged ≥ 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach. AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI. In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP.
MeSH Terms
- Academic Medical Centers
- Acute Disease
- Adrenomedullin
- Aged
- Aged, 80 and over
- Aging
- Atrial Natriuretic Factor
- Biomarkers
- Emergency Service, Hospital
- Endothelin-1
- Female
- Glycopeptides
- Heart Failure
- Humans
- Male
- Natriuretic Peptide, Brain
- Peptide Fragments
- Predictive Value of Tests
- Prognosis
- Prospective Studies
- Protein Precursors
- Reproducibility of Results
- Sensitivity and Specificity
- Severity of Illness Index
Keywords
- adrenomedullin
- aged
- diagnosis
- endothelin
- heart failure
- natriuretic peptides
Motor unit number estimation (MUNE) is a tool for estimating the number of motor units. The aim was to evaluate the multipoint incremental MUNE method in a healthy population, to analyze whether aging, gender, and the dominant hand side influence the motor unit number, and to assess reproducibility of MUNE with the Shefner modification. We studied 60 volunteers (mean age, 47 ± 17.7 years) in four groups aged 18 to 30, 31 to 45, 46 to 60, and above 60 years. Motor unit number estimation was calculated in the abductor pollicis brevis (APB) and the abductor digiti minimi (ADM) by dividing the single motor unit action potential amplitude into the maximal compound motor action potential amplitude. Test-retest variability was 7%. The mean value of MUNE for APB was 133.2 ± 43 and for ADM was 157.1 ± 39.4. Significant differences in MUNE results were found between groups aged 18 to 30 and 60 years or older and between groups aged 31 to 45 and 60 years or older. Motor unit number estimation results correlated negatively with the age of subjects for both APB and ADM. Single motor unit action potential, reflecting the size of motor unit, increased with the age of subjects only in APB. Compound motor action potential amplitude correlated negatively with the age of subjects in APB and ADM. Significant correlations were seen between MUNE in APB or ADM and compound motor action potential amplitude in these muscles and the age of female subjects. A similar relationship was not found in males. Multipoint incremental MUNE method with the Shefner modification is a noninvasive, easy to perform method with high reproducibility. The loss of motor neurons because of aging could be confirmed by our MUNE study and seems to be more pronounced in females.
MeSH Terms
- Action Potentials
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Electric Stimulation
- Female
- Healthy Volunteers
- Humans
- Male
- Middle Aged
- Motor Neurons
- Recruitment, Neurophysiological
- Sex Characteristics
- Young Adult
Highly active antiretroviral therapy (HAART) changed the natural history of pediatric HIV infection. This review focuses on trends of HIV-associated cancers in childhood in the HAART era and analyses potential pathogenetic mechanisms. HAART reduced AIDS-defined-malignancies (ADM), but incidence of several non-ADM is increasing. HIV-associated immune activation and inflammation, promoting tumorigenesis, can only partially be reduced by HAART. In addition, HIV-infected children may undergo accelerated immune senescence that favors cancer development. How HAART affects this condition is an open question. Lastly, there is no evidence that prenatal exposure to HAART increases the risk of cancer in childhood, but long-term studies are needed.
MeSH Terms
- Antiretroviral Therapy, Highly Active
- Child
- HIV Infections
- Humans
- Neoplasms
Keywords
- Aging
- Children
- HAART
- HIV-related cancer
- Immune activation
The purpose of this study was to determine whether older adults compared with young adults exhibit impaired end-point accuracy during a two-finger task due to altered activation of the contributing synergistic muscles. Nine young (21.3 years ± 1.6 years, 4 men) and 9 older (73.1 years ± 6.4 years, 5 men) were instructed to accurately match the center of a target with concurrent abduction of the index and little fingers (synergistic two-finger task). The target comprised of 20% MVC and 200 ms. Visual feedback of the force trajectory and target was provided 1s after each trial. Subjects completed 40 trials and the last 10 were used for analysis. Endpoint accuracy was quantified as the normalized deviation from the target in terms of peak force (peak force error), time-to-peak force (time-to-peak force error), and a combination of the two (overall error). Motor output variability was quantified as the standard deviation and coefficient of variation (CV) of peak force and time to peak force. The neural activation of the involved synergist muscles (first dorsal interosseus (FDI) and abductor digiti minimi (ADM)) was quantified with the electromyography (EMG) amplitude (root mean square) and its frequency structure (wavelet analysis). Older adults exhibited significantly greater peak force (46.7 ± 10% vs. 24.9 ± 3.2%) and overall endpoint error (68.5 ± 9.7% vs. 41.7 ± 4.3%), whereas the time to peak force error was similar for the two age groups. Older adults also exerted greater peak force variability than young adults, as quantified by the CV of peak force (34.3 ± 3.5% vs. 24.1 ± 2.3%). The greater peak force error in older adults was associated with changes in the activation of the ADM muscle but not the FDI. Specifically, greater peak force error was associated with greater power from 13-30 Hz and lesser power from 30-60 Hz. These results, therefore, suggest that older adults compared with young adults exhibit impaired endpoint force accuracy during a two finger task because of altered activation of one of the synergist muscles.
MeSH Terms
- Adolescent
- Aged
- Aging
- Electromyography
- Feedback, Physiological
- Female
- Fingers
- Humans
- Male
- Muscle Contraction
- Muscle, Skeletal
- Psychomotor Performance
- Young Adult
This study examined changes in corticomotor excitability and plasticity after a thumb abduction training task in young and old adults. Electromyographic (EMG) recordings were obtained from right abductor pollicis brevis (APB, target muscle) and abductor digiti minimi (ADM, control muscle) in 14 young (18-24 yr) and 14 old (61-82 yr) adults. The training task consisted of 300 ballistic abductions of the right thumb to maximize peak thumb abduction acceleration (TAAcc). Transcranial magnetic stimulation (TMS) of the left primary motor cortex was used to assess changes in APB and ADM motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before, immediately after, and 30 min after training. No differences in corticomotor excitability (resting and active TMS thresholds, MEP input-output curves) or SICI were observed in young and old adults before training. Motor training resulted in improvements in peak TAAcc in young (177% improvement, P < 0.001) and old (124%, P = 0.005) subjects, with greater improvements in young subjects (P = 0.002). Different thumb kinematics were observed during task performance, with increases in APB EMG related to improvements in peak TAAcc in young (r(2) = 0.46, P = 0.008) but not old (r(2) = 0.09, P = 0.3) adults. After training, APB MEPs were 50% larger (P < 0.001 compared with before) in young subjects, with no change after training in old subjects (P = 0.49), suggesting reduced use-dependent corticomotor plasticity with advancing age. These changes were specific to APB, because no training-related change in MEP amplitude was observed in ADM. No significant association was observed between change in APB MEP and improvement in TAAcc with training in individual young and old subjects. SICI remained unchanged after training in both groups, suggesting that it was not responsible for the diminished use-dependent corticomotor plasticity for this task in older adults.
MeSH Terms
- Adolescent
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Analysis of Variance
- Electric Stimulation
- Electromyography
- Evoked Potentials, Motor
- Female
- Humans
- Male
- Middle Aged
- Motor Cortex
- Motor Skills
- Movement
- Muscle Contraction
- Muscle, Skeletal
- Neural Inhibition
- Neuronal Plasticity
- Neurons
- Practice, Psychological
- Regression Analysis
- Signal Processing, Computer-Assisted
- Thumb
- Transcranial Magnetic Stimulation
- Young Adult
In the present report, we extent our previous findings (Clark et al. in Neuropsychologia 42:105-122, 2004) on corticomotor facilitation associated with covert (observation and imagery) and overt execution (action imitation) of hand actions to better delineate the selectivity of the effect in the context of an object-oriented action. A second aim was to examine whether the pattern of facilitation would be affected by age. Corticomotor facilitation was determined in two groups of participants (young n = 21, 24 /- 2 years; old n = 19, 62 /- 6 years) by monitoring changes in the amplitude and latency of motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation. MEP responses were measured from both the first dorsal interosseous (FDI, task selective muscle) and the abductor digiti minimi (ADM) of the right hand while participants attended to four different video presentations. Each of four videos provided specific instructions for participants to either: (1) close their eyes and relax (REST), (2) observe the action attentively (OBS), (3) close their eyes and mentally simulate the action (IMAG), or (4) imitate the action (IMIT). The action depicted in the videos represented a male subject cutting a piece of material with scissors. In the young group, the pattern of results revealed selective facilitation in the FDI in conditions involving either covert (OBS and IMAG) or overt action execution (IMIT). In the ADM, only overt execution with action imitation was associated with significant MEP facilitation. In the old group, a similar pattern of results was observed, although the modulation was less selective than that seen in the young group. In fact, older individuals often exhibited concomitant facilitation in both the FDI and ADM during either covert (OBS and IMAG conditions) or overt action execution (IMIT condition). Taken together, these results further corroborate the notion that the corticomotor system is selectively active when actions are covertly executed through internal simulation triggered by observation or by motor imagery, as proposed by Jeannerod (Neuroimage 14:S103-S109, 2001). With aging, the ability to produce corticomotor facilitation in association with covert action execution appears to be largely preserved, although there seems to be a loss in selectivity. This lack of selectivity may, in turn, reflect age-related alterations in the function of the corticospinal system, which may impair the ability to individuate finger movements either in the covert or overt stage of action execution.
MeSH Terms
- Adult
- Aging
- Electromyography
- Evoked Potentials, Motor
- Female
- Hand
- Humans
- Imagination
- Imitative Behavior
- Male
- Motor Cortex
- Motor Neurons
- Movement
- Muscle, Skeletal
- Neural Conduction
- Neuropsychological Tests
- Photic Stimulation
- Pyramidal Tracts
- Reaction Time
- Transcranial Magnetic Stimulation
Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G substitution at position -1984 in the promoter region of the ADM gene likely increases transcription. We therefore investigated this polymorphism in relation to blood pressure and urinary sodium in a Chinese population. We genotyped 427 Chinese enrolled in a family-based population study. We measured blood pressure by conventional sphygmomanometry and ambulatory monitoring. The frequencies of the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In adjusted analyses, G allele carriers, compared to AA homozygotes, had significantly lower conventional (45.3 versus 48.5 mm Hg, P = 0.004) and 24-h (42.6 versus 44.3 mm Hg, P = 0.03) pulse pressures and urinary sodium excretion (143.8 versus 159.4 mmol/day, P = 0.03). In parents, but not offspring, both systolic pressure and pulse pressure were significantly (P<0.01) lower in G allele carriers. The genotypic difference in sodium excretion was consistent across the age range. In 68 informative offspring, transmission of the G allele was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P = 0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9 pmol/l, P = 0.10). In conclusion, in Chinese, the ADM -1984G allele is associated with lower sodium excretion and in older subjects also with lower systolic pressure and narrower pulse pressure.
MeSH Terms
- Adrenomedullin
- Aging
- Asian Continental Ancestry Group
- Blood Pressure
- China
- Female
- Gene Frequency
- Humans
- Male
- Middle Aged
- Parents
- Peptides
- Polymorphism, Single Nucleotide
- Pulse
- Reference Values
- Sodium
- Systole
To investigate if the vasoactive systems adrenomedullin (ADM) and endothelin-1 (ET-1) are expressed in human adipose tissues in children and in adults and to determine the distribution pattern of nitric oxide synthases (NOS). Subcutaneous, mesenterial and omental adipose tissue specimens taken from 15 children (age 0.5-16 y, median 6 y) and 13 adults (age 43-79 y, median 60 y) were analyzed. The body mass indices (BMI) were within the normal range. All patients were normotensive, and were free of infectious disease, and metabolic or endocrine disorders. The specimens were taken during elective laparotomies after informed consent was obtained. ADM, ET-1, the endothelial (eNOS) and inducible (iNOS) NOS as well as two housekeeping genes were measured using quantitative real-time PCR. ADM gene expression was found at all locations, and was significantly higher in adults than in children (P<0.01 for subcutaneous and omental adipose tissue). ET-1 mRNA was distributed in a similar way, showing significantly higher levels in the subcutaneous and mesenterial adipose tissue sections of adults than of children. For eNOS, the adult patients exhibited a higher expression in subcutaneous and mesenterial specimens than the children (P<0.01 and P<0.05). The iNOS mRNA was increased in subcutaneous, mesenterial and omental adipose tissues in the adult cohort compared to the children's levels (P<0.05 to P<0.01). Human adipose tissue expresses many vasoactive substances including ADM and ET-1. In adults, the amounts of ET-1 and ADM as well as eNOS and iNOS mRNA are higher, possibly due to a physiological upregulation with increasing age. Although there are differences depending on the locations of the tissues, the expression patterns of the antagonists ADM and ET-1 are quite similar, indicative of a well-balanced pattern of local gene expression in normotensive individuals with normal body weight.
MeSH Terms
- Adipose Tissue
- Adolescent
- Adrenomedullin
- Adult
- Aged
- Aging
- Body Mass Index
- Child
- Child, Preschool
- Endothelin-1
- Female
- Gene Expression Regulation, Developmental
- Humans
- Infant
- Male
- Mesentery
- Middle Aged
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Omentum
- Peptides
- RNA, Messenger
- Subcutaneous Tissue
In order to determine the utility of motor unit number estimation (MUNE) in assessing axonal loss in chronic inherited neuropathies, we determined MUNEs in 54 patients with Charcot-Marie-Tooth (CMT) disease (29 patients with CMT-1A, 13 with CMT-X, and 12 with CMT-2) by using spike-triggered averaging (STA) of the ulnar-innervated abductor digiti minimi/hypothenar muscles (ADM) and the musculo-cutaneous innervated biceps/brachialis (BB) muscles. MUNEs were analyzed in relationship to the corresponding compound muscle action potential (CMAP) amplitudes as well as to clinical strength. Proximal muscles, which appeared strong clinically, had evidence of chronic denervation/reinnervation, although to a lesser extent than weak distal hand muscles, supporting the concept that axonal loss in CMT occurs in a length-dependent fashion. The reduction in ADM-MUNE strongly correlated with clinical weakness in the hand. Both the ADM-MUNE and BB-MUNE were abnormal more often than CMAP amplitude, probably reflecting extensive motor unit reconfiguration and enlargement that maintains CMAP amplitude despite severe motor unit loss. This study suggests that MUNE can assess motor unit loss in CMT and may better reflect axonal loss than CMAP amplitude. The STA technique of MUNE may be useful in longitudinal studies of proximal and distal motor unit changes in CMT.
MeSH Terms
- Action Potentials
- Adolescent
- Adult
- Aged
- Aging
- Cell Count
- Charcot-Marie-Tooth Disease
- Electric Stimulation
- Electrophysiology
- Female
- Humans
- Male
- Middle Aged
- Motor Neurons
- Muscle, Skeletal
A method for the in vivo measurement of light transparency of the human crystalline lens, based on the measurement of the blue and red light threshold radiance, in presented. The threshold limit values for radiances of 477 nm (blue) and 620 nm (red) were measured for people at age from 17 to 66 years old without cataract. The people recognised the geometric figures by left and right eye separately, after being adapted to darkness. The radiance of the figures was changed smoothly by ADM adaptometer. The threshold limit values were measured several times for each eye. For each eye the average of the threshold limit values for radiances of 620 nm and 477 nm and their quotient were calculated. Values of these quotients practically did not change for young eyes (to 32 years old) and they decreased for older eyes. These results indicate the increase of the threshold radiance of 477 nm in relation to threshold radiance of 620 nm for older people, and this means the reduction of the crystalline lens transparency for blue light in relation to red one as they grow old. It seems that the reduction should precede the development of cataractous changes and this fact may be used in the diagnostics of precataractous states.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Cataract
- Female
- Humans
- Lens, Crystalline
- Light
- Male
- Middle Aged
- Reference Values
The purpose of this study was to determine if masseter muscle endurance changes with increasing age and, if so, to examine mechanisms of fatigue. Characteristics of fatigue were measured under isometric conditions using high-frequency stimulation of anterior deep masseter (ADM) muscles of male Fischer 344 rats, 5 to 24 months old, and fed a hard (HD) or a soft (SD) diet. Potentiating effects of caffeine on ADM muscle performance in vitro were also examined. Fatigability increased by 48% with age in muscles of HD rats. Muscles of SD rats were highly fatigable at all ages. Increased HD fatigability was associated with significantly decreased concentrations of Na /K -adenosine triphosphatase (22%) and decreased responsiveness to caffeine postfatigue (29%). The pH levels decreased similarly in fatigued muscles of all groups. We conclude that the age-related increase in fatigability is associated with alterations in excitation-contraction coupling mechanisms. However, differences between SD and HD on ADM muscles represent possible fiber-type transitions.
MeSH Terms
- Aging
- Animals
- Caffeine
- Diet
- Hydrogen-Ion Concentration
- Male
- Masseter Muscle
- Muscle Contraction
- Muscle Fatigue
- Osmolar Concentration
- Physical Endurance
- Potassium
- Rats
- Rats, Inbred F344
- Sodium-Potassium-Exchanging ATPase
- Solutions
The role of coronary flow in the regulation of ventricular B-type natriuretic peptide (BNP) gene expression was studied in isolated perfused rat heart preparation. The increase of coronary flow from 5 ml/min to 20 ml/min for 2 h resulted in a 132 /-6 mm Hg increase in aortic perfusion pressure. The changes in BNP mRNA and immunoreactive BNP (IR-BNP) levels in response to hemodynamic stress were compared to those of c-fos and adrenomedullin (ADM) gene expression. The increase of coronary flow resulted in 1.5-fold increases in the left ventricular BNP mRNA (P < 0.001) and IR-BNP (P < 0.05) levels in 2-month old rats. There was also a 1.5-fold (P < 0.05) increase in ventricular c-fos mRNA levels, whereas ADM mRNA levels decreased by 74% (P < 0.001) in the left ventricle. In 18-month old rats, the increase in coronary flow decreased left and right ventricular BNP mRNA levels by 18% (P < 0.05) and 39% (P < 0.001), respectively. There were no changes in IR-BNP peptide and c-fos mRNA levels, whereas ADM mRNA levels decreased by 46% (P < 0.001) in the left ventricles. The results show that increased aortic perfusion pressure results in differential expression of cardiac genes including up-regulation of ventricular BNP and c-fos gene expression and down-regulation of ADM gene expression. Furthermore, aging seems to elevate the threshold at which hemodynamic stress of the heart results in a response at BNP gene level.
MeSH Terms
- Adrenomedullin
- Aging
- Animals
- Atrial Natriuretic Factor
- Central Venous Pressure
- Coronary Circulation
- Coronary Vessels
- Cytoplasm
- Gene Expression Regulation
- Heart Ventricles
- Immunohistochemistry
- In Vitro Techniques
- Male
- Myocardium
- Natriuretic Peptide, Brain
- Peptides
- Perfusion
- RNA
- Rats
- Rats, Inbred WKY
- Rats, Sprague-Dawley
Adriamycin (ADM), an antineoplastic antibiotic, when injected intramuscularly, is taken up by motoneuron axonal terminals and retrogradely transported to the motoneuron soma where it exerts its neurotoxic effect. In the present study, ADM was injected into the hindlimb muscles of five adult cats. Measurements of the electrophysiological properties of the lumbar motoneurons innervating these muscles were obtained using intracellular techniques. Based upon these data the equivalent cylinder model of motoneurons was employed to evaluate ADM-induced changes in cell size and cell geometry. The size of cell somas in the ventral horn was also measured using light microscopy and computer imaging software. There were significant increases in the membrane time constant (25%) and input resistance (50%) in motoneurons whose muscles were treated with ADM (ADM-MNs) compared with data from control motoneurons (control-MNs). The increase in membrane time constant is attributed to an increase in membrane resistance; the increase in input resistance appears to depend upon both an increase in membrane resistance and a decrease in total cell surface area. Cell capacitance, which is proportional to the total cell surface area, was significantly reduced (15%) in ADM-MNs. Calculations based on cable theory indicate that while there was no significant change in the length of the equivalent cylinder for ADM-MNs, there was a significant decrease (17%) in the diameter of the equivalent cylinder. These data indicate that there is a decrease in total cell surface area which can be attributed to the shrinkage of branches throughout the dendritic tree. There was also a small (7%) but statistically significant decrease in the electrotonic length of ADM-MNs. Morphological analysis also revealed that the mean cross-sectional area of the somas of those ventral horn neurons which are likely to correspond to the motoneuron population was significantly reduced on the ADM-treated side compared to that of neurons on the control side. We conclude that significant geometrical changes were induced in lumbar motoneurons of adult cats after ADM was injected to their muscles. In old cats, spinal cord motoneurons exhibit similar patterns of changes in their electrophysiological characteristics which have also been suggested to be correlated with changes in cell geometry. The question then arises as to whether the response of motoneurons to ADM and the aging process reflects a stereotypic reaction of motoneurons to a variety of insults or whether the response to ADM mirrors specific aspects of the aging process.
MeSH Terms
- Aging
- Animals
- Cats
- Cell Count
- Doxorubicin
- Electric Conductivity
- Electric Impedance
- Injections, Intramuscular
- Mathematics
- Motor Neurons
- Spinal Cord
- Time Factors
1. This study was undertaken to investigate the effects of adriamycin (ADM, Doxorubicin) on the basic electrophysiological properties of spinal cord motoneurons in the adult cat. ADM was injected into the biceps, gastrocnemius, semitendinosus, and semimembranosus muscles of the left hindlimb (1.2 mg per muscle). Intracellular recordings from motoneurons innervating these muscles were carried out 12, 20, or 40 days after ADM administration and from corresponding motoneurons in untreated control cats. 2. Twelve days after ADM injection, motoneurons innervating ADM-treated muscles (ADM MNs) exhibited statistically significant increases in input resistance, membrane time constant, and amplitude of the action potential's afterhyperpolarization (AHP). In addition, there was a statistically significant decrease in rheobase and in the delay between the action potential of the initial segment (IS) and that of the somadendritic (SD) portion of the motoneuron (IS-SD delay). There were no significant changes in the resting membrane potential, threshold depolarization, action potential amplitude, or axonal conduction velocity. 3. The changes in electrical properties of motoneurons at 20 and 40 days after ADM injection were qualitatively similar to those observed at 12 days. However, at 40 days after ADM injection there was a statistically significant decrease in the axonal conduction velocity of the ADM MNs. 4. The normal correlations that are present between the AHP duration and electrical properties of the control motoneurons were observed in the ADM MNs, e.g., AHP duration was positively correlated with the input resistance and time constant and negatively correlated with the axonal conduction velocity. The correlation coefficients, however, were reduced in comparison with the control data. 5. This study demonstrates that ADM exerts significant effects on the electrical properties of motoneurons when injected into their target muscles. The majority of the changes in motoneuron electrical properties caused by ADM resemble those observed in motoneurons of aged cats. Additional research is required to determine whether the specific changes induced in motoneurons by ADM and those that occur in motoneurons in old age are due to similar degradative mechanisms.
MeSH Terms
- Action Potentials
- Aging
- Animals
- Cats
- Doxorubicin
- Electric Impedance
- Hindlimb
- Injections, Intramuscular
- Membrane Potentials
- Motor Neurons
- Spinal Cord