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Biomedical subjects

R Baratta

Publications and source records attributed to R Baratta.

At least 19 recordsLinked to original sources
PubMed2003

Evidence for genetic epistasis in human insulin resistance: the combined effect of PC-1 (K121Q) and PPARgamma2 (P12A) polymorphisms.

Insulin resistance is believed to be under the control of several genes often interacting each other. However, whether genetic epistasis does in fact modulate human insulin sensitivity is unknown. In 338 healthy unrelated subjects from Sicily, all nondiabetic and not morbidly obese, we investigated whether two gene polymorphisms previously associated with insulin resistance (namely PC-1 K121Q and PPARgamma2 P12A) affect insulin sensitivity by interacting. PC-1 X121Q subjects showed higher level of fasting glucose, lower insulin sensitivity (by both the Matsuda insulin sensitivity index and M values at clamp, the latter performed in a subgroup of 113 subjects representative of the overall cohort) and higher insulin levels during the oral glucose tolerance test (OGTT) than PC-1 K121K subjects. In contrast, no difference in any of the measured variables was observed between PPARgamma2 P12P and X12A individuals. The deleterious effect of the PC-1 X121Q genotype on each of these three variables was significant and entirely dependent upon the coexistence of the PPARgamma2 P12P genotype. Among PPARgamma2 P12P carriers also fasting insulin and glucose levels during OGTT were higher in PC-1 X121Q than in K121K individuals. In contrast, no deleterious effect of the PC-1 X121Q genotype was observed among PPARgamma2 X12A carriers; rather, in these subjects a lower body mass index and consequently lower fasting insulin level was observed in PC-1 X121Q than in K121K carriers. Overall, a significant interaction between the two genes was observed on body mass index, insulin levels (both fasting and after OGTT) and both insulin sensitivity (i.e., insulin sensitivity index and M value) and insulin secretion (i.e., HOMA-B%) indexes.

Adult↗
PubMed2001

The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance.

PC-1 is a membrane glycoprotein that impairs insulin receptor function. Its K121Q polymorphism is a genetic determinant of insulin resistance. We investigated whether the PC-1 gene modulates insulin sensitivity independently of weight status (i.e. both in nonobese and obese individuals). Nondiabetic subjects [164 males, 267 females; age, 37 +/- 0.6 yr, mean +/- SEM; body mass index (BMI), 32.7 +/- 0.5 kg/m(2)], who were subdivided into 220 nonobese (BMI < or = 29.9) and 211 obese, were studied. Although subjects were nondiabetic by selection criteria, plasma insulin concentrations during oral glucose tolerance test were higher (P < 0.05) in Q allele-carrying subjects (K121Q or Q121Q genotypes), compared with K121K individuals, in both the nonobese and obese groups. Insulin sensitivity, measured by euglycemic clamp in a representative subgroup of 131 of 431 randomly selected subjects, progressively decreased (P < 0.001) from nonobese K121K [n = 61; glucose disposal (M) = 34.9 +/- 1.1 micromol/kg/min] to nonobese Q (n = 21; M = 29.9 +/- 2.0), obese K121K (n = 31, M = 18.5 +/- 1.2), and obese Q (n = 18, M = 15.5 +/- 1.2) carriers. The K121Q polymorphism was correlated with insulin sensitivity independently (P < 0.05) of BMI, gender, age, and waist circumference. In conclusion, the Q121 PC-1 variant and obesity have independent and additive effects in causing insulin resistance.

Adolescent↗
PubMed1999

The intravenous insulin tolerance test is an accurate method for screening a general population for insulin resistance and related abnormalities.

To verify whether the short intravenous insulin tolerance test (ITT) (a safe, reproducible, inexpensive, rapid and easy to perform measurement of insulin sensitivity) is a suitable test for insulin resistance screening in a general population, we measured in 60 non diabetic subjects, either non-obese (no.=40) or obese (BMI>28, no.=20) the K of glucose disappearance from plasma after ITT (K(ITT)), plasma glucose (PG) and insulin (IRI) both fasting (FPG, FIRI) and at 120 min of OGTT (PG- 120, IRI- 120), and also triglycerides (Tg), cholesterol (Chol) and blood pressure (BP). Subjects were subdivided into quartiles according to K(ITT) values. Average FPG, PG-120, FIRI, IRI-120, Tg and Chol values were progressively increased, and average HDL/Chol was progressively decreased from quartile 1 (the most insulin sensitive) to 4 (the most insulin resistant) (p<0.05, by 1-way ANOVA test). Also BP was increased in the insulin resistant patients, but statistical significance was not reached. Three or more of the studied parameters (FPG and/or PG-120, FIRI and/or IRI-120, Tg, HDL/Chol, mean BP) were altered (below the worst 25 degree percentile) in 64% of subjects from quartile 4; none of the subjects in quartile 1 was affected by such a cluster of alterations. K(ITT) values < or =4.8 identified the cluster of insulin resistance related alterations with an accuracy of 82% (sensitivity=83.3%, specificity=80.5%). In healthy subjects with a wide range of BMI the ITT is a reliable procedure for screening for the cluster of metabolic alterations related to insulin resistance.

Adolescent↗
PubMed1999

A soluble PC-1 circulates in human plasma: relationship with insulin resistance and associated abnormalities.

An increased tissue content of PC-1, an inhibitor of insulin receptor signaling, may play a role in insulin resistance. Large scale prospective studies to test this hypothesis are difficult to carry out because of the need for tissue biopsies. The aim of this study was to investigate whether PC-1 is measurable in human plasma and whether its concentration is related to insulin sensitivity. A soluble PC-1, with mol wt and enzymatic activity similar to those of tissue PC-1, was measurable in human plasma by a specific enzyme-linked immunosorbent assay and was inversely correlated to skeletal muscle PC-1 content (r = -0.5; P < 0.01). The plasma PC-1 concentration was decreased (P < 0.05) in insulin-resistant (22.7 +/- 3.0 ng/mL; n = 25) compared to insulin-sensitive (36.7 +/- 4.5; n = 25) nondiabetic subjects and was correlated negatively with the waist/hip ratio (r = -0.48; P < 0.001) and mean blood pressure (r = -0.3; P < 0.05) and positively with high density lipoprotein/total cholesterol (r = 0.38; P < 0.01) and both the M value and the plasma free fatty acid level decrement at clamp studies (r = 0.28; n = 50; P = 0.05 and r = 0.43; n = 22; P < 0.05, respectively). A plasma PC-1 concentration of 19 ng/mL or less identified a cluster of insulin resistance-related alterations with 75% accuracy. In conclusion, PC-1 circulates in human plasma, and its concentration is related to insulin sensitivity. This may help to plan studies aimed at understanding the role of PC-1 in insulin resistance.

Adult↗
PubMed1999

A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.

The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.

Adult↗
PubMed1997

Accuracy of formula-derived creatinine clearance in paraplegic subjects.

The usefulness of formula-derived creatinine clearance (CC) is not well established among the paraplegic population. We prospectively collected 24-hour-urines from paraplegic subjects, obtaining 81 collections from 42 patients over 27 months. After validation, 57 collections were used to obtain measured CC. CCs were also estimated using several formulae. Measured CC and estimated CC were then compared. In the case of the Cockroft-Gault formula, the overall correlation was excellent, with an r value of 0.88 and p = 0.0001. In our study 40, 70, and 93% of the estimated CCs were within 10, 20, and 33% of the measured CCs. These numbers are similar to the ones reported by Cockroft and Gault. Also, the data on measured creatinine clearance in paraplegics compared favorably with parallel data obtained from nonparaplegics (91 24-hour-urine collections, 65 validated). We conclude that the Cockroft-Gault formula (and other formulae) estimate creatinine clearance as accurately in the paraplegic population as they do in the nonparaplegic population.

Adult↗
PubMed1996

Motor unit recruitment strategy changes with skill acquisition.

The modifications of motor unit recruitment strategy due to skill acquisition was determined in the elbow flexor-extensor muscles of normal human subjects. The median frequency of the power density spectra of the electromyograms recorded from the biceps and triceps muscles during a 3-s linear increase in flexion force in the range of 0-100% maximal voluntary contraction (MVC) was calculated for each subject, every 2 weeks over a total 6-week period during which subjects practiced linear flexion force increase three times a week. Electromyograms were recorded with two pairs of electrodes of different size and electrode spacing. It was shown that skill acquisition due to the 360 practice trials over the 6-week period caused an increase in the initial motor unit recruitment phase of the agonist's force generation cycle from about 0-65% MVC to about 0-85% MVC. The increase in the recruitment range was gradual and statistically significant for the measurements made every 2 weeks. The recruitment range of the antagonist triceps demonstrated a minor, but statistically insignificant, decrease over the same training period. There was a minor, but statistically insignificant, advantage of using small electrodes and inter-electrode spacing. It was concluded that skill acquisition, due to repeated functional use of a muscle in the same contraction mode, results in a slower, prolonged recruitment of motor units in the initial segment of the force generation cycle, thereby allowing a more precise and accurate control of the increments of force increase. Such conclusions reinforce the concept advocating the plasticity of motor unit control according to the functional demands imposed on the muscle. The results have significant implications in the design of various athletic, occupational and rehabilitation training modalities for optimal performance of various movement functions.

Adult↗
PubMed1996

Energy expenditure and fatiguability in paraplegic ambulation using reciprocating gait orthosis and electric stimulation.

To clarify the relationship between metabolic energy expenditure and fatiguability in paraplegic persons fitted with orthoses, we measured energy consumption in six thoracic paraplegic patients ambulating by means of reciprocating gait orthosis (RGO) used with and without functional electrical stimulation (FES). The data obtained from persons using both RGO and FES were adjusted to allow for the effects of fatiguability so as to obtain an approximate value for upper-body consumption. The data obtained from persons using RGO only were not adjusted, because no energy consumption occurred in the lower portion of the body. The data, expressed in kcal/kg-min and kcal/kg-m, were plotted against walking speed attained using RGO, and RGO with FES. The results were compared with those from persons fitted with long leg braces (LLB), hip guidance orthoses (HGO) and an FES walking aid (data obtained from available literature). We found that the lowest energy expenditure in kcal/kg-m across the full range of walking speeds occurred when both RGO and FES were used together, followed by RGO only, HGO, LLB, and FES only, respectively. The lowest energy expenditure in kcal/kg-min, for walking speeds, below 0-28 m/s, also occurred when both RGO and FES were used together, followed by RGO only, HGO, LLB, and FES only. The results suggest that, although the use of FES with RGO may increase oxygen uptake, it decreases energy expenditure in the upper extremities, thereby reducing patient fatigue. They also suggest that mechanical orthosis giving passive support to the hip, knee and ankle in combination with FES may provide the most efficient walking aid for paraplegic persons.

Adult↗
PubMed1995

Dynamic performance model of an isometric muscle-joint unit.

The dynamic performance model of the medial gastrocnemius muscle of the cat was determined when generating isometric force at its tendon and when transmitting that force across the joint. The frequency response model of the muscle and of the muscle-joint was developed by fitting the experimentally obtained gain and phase Bode plots with a best fit linear second order system determined by recursive least squares. It was shown that the muscle could be represented with double poles at 2.3 Hz and a time delay of 16 ms whereas the muscle-joint was represented with an additional pole at 1.8 Hz, a zero at 3.8 Hz and 16 ms time delay. The harmonic distortion was less than 5% for sinusoidal force output in the frequency range of 0.4-4 Hz, and a force range of 20-80% of the maximal justifying a linear system model. The model is useful in the design of a neuromuscular prosthesis, using electrical stimulation of the muscle nerves, as a rehabilitation procedure for paralysed patients due to spinal cord injury.

Animals↗
PubMed1995

The glenohumeral-biceps reflex in the feline.

The existence of a reflex arc from the anterior aspects of the glenohumeral capsule to the long head of the biceps was determined in a feline. A single articular branch of the musculocutaneous nerve terminating in the capsule was identified and stimulated with 100 microseconds supramaximal pulse train at 10 pulses per second. It was shown tht stimulation of the musculocutaneous articular nerve elicited myoelectric discharge in the biceps muscle. Transection of the articular nerve just distal to its emergence from the main trunk of the musculocutaneous nerve abolished the myoelectric discharge in the biceps, confirming the afferent nature of this articular nerve. The mean (+/- standard deviation) time delay from the application of the stimulus to the articular nerve to the recording of the corresponding myoelectric discharge in the biceps was 2.7 (+/- 0.3) milliseconds. The existence of a reflex arc from the capsule to the biceps confirms and extends the concept of passive (ligaments) and active (muscles) restraints of a joint and the synergy between them toward maintaining shoulder stability. If demonstrated in the human, such a reflex may have significant implications in modification of surgical procedures and the design of new rehabilitation modalities for treatment of shoulder defects.

Action Potentials↗
PubMed1994

Comparison of isometric and load moving length-tension models of two bicompartmental muscles.

The length-tension relations of two bicompartmental muscles, including parallel and pennated fibers, were experimentally determined for isometric and load moving contractions. Comparison of the isometric and constant mass load length-tension curves obtained from the same preparations demonstrated significant reductions in force, a shift of the optimal length and increased elongation range for shortening contractions under constant mass load. Pennated muscle demonstrated a larger reduction in force and greater shift in the optimal length relative to the changes in a muscle with parallel fibers. A bicompartmental model was fitted to the experimental data to provide quantitative insight to the changes described above, and for use in mathematical models of other bicompartmental muscles, and for design of optimal electrical stimulation system for restoration of function in spinal cord injury patients.

Animals↗
PubMed1992

The isometric length-force models of nine different skeletal muscles.

The length-force relations of nine different skeletal muscles in the hindlimb of the cat were determined experimentally, with electrical stimulation of the sciatic nerve as the activation mode. It was shown that the active-, passive-, and total-force patterns varied widely among the muscles. The tibialis posterior (TP), medial and lateral gastrocnemius (MG, LG) and flexor digitorum longus (FDL) had a symmetric active-force curve, whereas the tibialis anterior (TA), peroneus brevis (PB), peroneus longus (PL), extensor digitorum longus (EDL), and soleus (SOL) had an asymmetric curve which exhibits about 25% of the maximal isometric force at extreme lengths. The SOL, EDL, and LG had a low-level passive force which appeared at short muscle length, whereas all other muscles exhibited initial passive force just before the optimal length. The total force was rising quasi-linearly for the SOL, whereas the other muscles exhibited an intermediate plateau about the optimal length. The LG and FDL had a substantial but temporary intermediate dip in the total force as the muscle was elongated past the optimal length. The elongation range of the various muscles also varied, ranging from +/- 15 to +/- 30% of the optimal length. The elongation range was symmetric for the FDL, LG, MG, TP, SOL, and EDL, and asymmetric for the PL, PB, and TA, being -12 to + 17%, -12 to + 17%, and -35 to + 12%, respectively. Two different models which incorporate muscle architecture were successfully fitted to the experimental data of the muscles except for the MG and TA. The architecture of these two muscles is highly nonhomogeneous and contains compartments with two pennation patterns or two different optimal lengths. New models, which add spatially and temporally the individual characteristics of each compartment of the muscles, were constructed for these two muscles. The new models demonstrated high correlation to the experimental data obtained from the MG and TA. It was concluded that the length-force relation varies widely among various skeletal muscles and is probably dependent on the primary function of the muscle in the context of integrated movement; this is a manifestation of architectural factors such as fiber pennation pattern and angle, cross-sectional area, ratio of muscle to tendon length, distribution of the fiber length within the muscle and compartmental pennation.

Animals↗
PubMed1991

The effect of tendon viscoelastic stiffness on the dynamic performance of isometric muscle.

The effect of tendons viscoelastic stiffness on the dynamic response of the cat's tibialis anterior muscle under isometric conditions was determined. It was shown that the dynamic response model of the muscle derived under sinusoidal contraction-relaxation in the range of 20-80% of its maximal isometric tension was not statistically different before and after the disection of the whole distal tendon. It was suggested that under isometric conditions in the force range of 20-80% of the maximal, the tendon acts as a very stiff force transmission linkage without significantly modifying the muscle's performance.

Animals↗
PubMed1991

Dynamic performance of a load-moving skeletal muscle.

The dynamic response of the tibialis anterior muscle of the cat was determined while it was subjected to sinusoidally varying orderly stimulation of motor units and to different isotonic loads in the range of 14-85% of the maximal isometric force. The dynamic response consisted of three major components: the displacement gain, the displacement attenuation, and a pure time delay. The displacement gain was dependent on the passive load applied to the muscle and the active force generated during contraction, which could be determined from the length-tension relationships and the corresponding shortening velocity. In general, the load displacement decreased as the load mass increased from 25 to 85% of the maximal isometric force. For loads less than 25% of the maximal isometric force, slight decrease in displacement was consistently observed. The displacement attenuation was dependent on the contraction frequency but uniform for all the load masses applied to the muscle. A pure time delay of 5 ms was present and accounted for various physiological processes such as conduction time in nerve and muscle, neuromuscular junction transmission, and excitation-contraction coupling. A quantitative equation was developed to describe the muscle's dynamic response under isotonic conditions and for a wide range of loads for use in various applications.

Animals↗
PubMed1990

The dynamic response model of nine different skeletal muscles.

The frequency response model of nine different skeletal muscles in the hindlimb of the cat was determined with the aide of electrical nerve stimulation which allows orderly stimulation of motor units concurrently with firing rate increase. It was shown that the general model consists of a linear second-order system with double real poles and a pure time delay. The pole values were different for the different muscles, ranging from 1.55 to 2.8 Hz. Similarly, the pure time delay varied from muscle to muscle, ranging from 8 to 17 ms. Statistical analysis demonstrates that under isometric contraction with force oscillations in the range of 10-90% of maximal the model poles are determined, and could be predicted, from the muscles functional and anatomical location in the limb and from its pennation pattern.

Animals↗
PubMed1990

Electromyogram power spectra frequencies associated with motor unit recruitment strategies.

The isolated contributions of motor unit recruitment and firing rate variations to the median frequency of the electromyogram's power density spectrum were determined. Orderly stimulation of the cat gastrocnemius motor units via nerve electrodes gave rise to linearly increasing median frequency regardless of the action potential firing rate of the active motor units. Increase in the discharge rate of all the motor units resulted in nearly constant median frequency. It was concluded that the increasing average conduction velocity during motor unit recruitment is the major contributor to variations in the electromyogram median frequency. The possibility of using the median frequency as the index to identify the recruitment control strategies employed by various muscles during increasing force contraction is suggested.

Action Potentials↗
PubMed1989

Frequency response model of skeletal muscle: effect of perturbation level, and control strategy.

The frequency response model of the soleus muscle of the cat was determined as a function of various firing rate and recruitment control strategies and at various force oscillation levels. We found that the basic frequency response models of the muscle during individual force oscillations at various control strategies in which the motor unit population of the muscle was fully recruited to obtain 50 per cent and up to 100 per cent of the maximum force, either concurrently with firing rate increase or at constant firing rate, were nearly identical. The model consisted of a second-order, linear low-pass filter with double poles at 1.85 Hz and a pure time delay of 16 ms. The model resulting from only firing rate increase from the frequency of fusion of the smallest motor unit to the maximum tetanic rate of the muscle while all the motor units were continuously active was nonlinear, and depended on the force's oscillation level. This nonlinear response of the rate coding process is also identified as the source of the increased harmonic distortion in the model where the initial 50 per cent of the force was generated by fully recruiting all the motor units, and the final 50 per cent of the force was generated by firing rate increase. We concluded that the basic frequency response model of a muscle under conditions similar to voluntary contraction consists of a linear, second-order system which is robust and independent of control strategy and force perturbation level.

Animals↗