Some physiological and behavioural changes associated with oestrus and pregnancy in the squirrel monkey (Satmiri sciureus)

Peak values in the karyopyknotic index of vaginal smears from the squirrel monkey occurred at intervals of 10.9±0.1 days. The urinary excretory rate of a metabolite similar to preg-nanediol increased when ovulation was induced by exogenous gonadotropin therapy. Small amounts of this metabolite were excreted during lactation, periods of anoestrus and during the follicular phases of normal oestrous cycles. Significantly larger amounts were excreted during the 157 days gestation period and during the luteal phase which persisted for one week after a peak karyopyknotic index value was observed. Changes in the pattern of urinary electrolyte excretion were not correlated reliably with changes in ovarian differentiation. Sexual motivation was greatest at mid-cycle, became less after conception and persisted at a low level throughout gestation and lactation. The occurrence of oestrus was seasonal and independent of physical contact with males. The development of secondary sexual characteristics in the male was synchronized with the onset of seasonal oestrus in the females.     

Hormonal and behavioral changes at puberty in the squirrel monkey

Developmental changes in the reproductive behavior and physiology of 9 male and 15 female juvenile squirrel monkeys were evaluated in a 20-month study. Plasma levels of gonadal steroids remained relatively low for this species until most animals reached puberty between 2.5 and 3 years of age. Longitudinal assessment of plasma progesterone levels indicated that the onset of ovarian cycles tended to be synchronized between females although the 5 heaviest females began to cycle earlier than the rest. The heavier females reached puberty at a time which was appropriate to their birth in the wild, whereas most of the remaining females conceived 6 months later during a second period of reproductive activity that coincided with the laboratory mating season. Pubescent males underwent their first seasonal elevation in plasma testosterone levels during the second period and its onset was synchronized across all males. Thus, even in the absence of adults, pubertal processes in the squirrel monkey were strongly influenced by the seasonal breeding pattern. In addition, behavioral observations revealed that social maturation closely parallels reproductive ability in females, whereas males enter a protracted subadult stage after puberty.     

Pathogen-induced heart rate changes associated with cholinergic nervous system activation

The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.     

Right heart structural changes are independently associated with exercise capacity in non-severe COPD

Background

Pulmonary hypertension (PH) occurs frequently and results in functional limitation in advanced COPD. Data regarding the functional consequence of PH in less severe COPD are limited. Whether echocardiographic evidence of right sided heart pathology is associated with functional outcomes in patients with non-severe COPD is unknown.

Methods

We evaluated pulmonary function, six minute walk distance, and echocardiography in 74 consecutive patients with non-severe COPD. We performed multivariable linear regression to evaluate the association between right heart echocardiographic parameters and six minute walk distance adjusting for lung function, age, sex, race, and BMI.

Main Results

The mean six minute walk distance was 324±106 meters. All subjects had preserved left ventricular (LV) systolic function (LV ejection fraction 62.3%±6.1%). 54.1% had evidence of some degree of diastolic dysfunction. 17.6% of subjects had evidence of right ventricular enlargement and 36.5% had right atrial enlargement. In univariate analysis RV wall thickness (β = −68.6; p = 0.002), log right atrial area (β = −297.9; p = 0.004), LV mass index (β = −1.3; p = 0.03), E/E'' ratio (β = −5.5; p = 0.02), and degree of diastolic dysfunction (β = −42.8; p = 0.006) were associated with six minute walk distance. After adjustment for co-variables, the associations between right atrial area (log right atrial area β = −349.8; p = 0.003) and right ventricular wall thickness (β = −43.8; p = 0.04) with lower six minute walk distance remained significant independent of forced expiratory volume in one second (FEV1). LV mass index, E/E'' ratio, and degree of diastolic dysfunction were not independent predictors of six minute walk distance.

Conclusion

In patients with non-severe COPD right sided cardiac structural changes are associated with lower six minute walk distance independent of lung function. These findings may indicate that echocardiographic evidence of pulmonary hypertension is present in patients with non-severe COPD and has important functional consequences.     

Dog and human acid beta-D-galactosidases are structurally similar.

The purification of dog liver acid beta-galactosidase is described. The dog enzyme migrated as a single major band on polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, with a molecular weight of 60000. Antiserum raised against purified human liver acid beta-galactosidase cross-reacted with beta-galactosidase from dog liver, but not with those from cat liver or Escherichia coli. Tryptic peptide maps of the dog and human acid beta-galactosidases indicate that 21 of the 24 peptides observed were homologous; a similar result was obtained after chymotryptic peptide mapping. We conclude that dog and human acid beta-galactosidases are structurally similar, and that canine GM1 gangliosidosis (acid beta-galactosidase deficiency) is an excellent model for the same disease in man.     

Developmental changes of the glycolytic enzymes in the human fetal heart

The ontogeny of hexokinase, phosphofructokinase, phosphoglucoisornerase, aldolase, pyruvate kinase and lactate dehydrogenase activities which are associated with glycolysis, an important energy yielding process, has been studied in human fetal heart for periods ranging from 13 weeks to above 33 weeks of gestation. Hexokinase, phosphoglucoisomerase and pyruvate kinase activities show similar developmental profiles exhibiting maximum activity at 25–28 weeks ofgestation. Phosphofructokinase activity, on the other hand, shows a minimum at this period and exhibits a peak value at early stages (13–16 weeks of gestation). Though considerable activity for aldolase is observed at an early period, it declines thereafter, but again increases in the later period. The probable role and correlations of these glycolytic enzymes with energy demand and general functional development in human fetal heart in ontogeny are evaluated.     

Analysis of changes in heart rate and temperature of the ground squirrel Citellus undulatus in various physiological states

Heart rate (HR) of ground squirrel C. undulatus was studied in dependence of season, level of activity, physiological state and air temperature (T). In summer HR varies from 110-130 beat/min in sleep up to 420 beat/min at flight from danger. During winter hibernation HP was minimal (3-5 beat/min) at T 1-4 degrees C, the increase in T induced the growth of HP in correspondence to the Arrenius van't Hoff law. The temperature of the body in hibernation exceeded T on 1.5-3 degrees C. The time of getting off the hibernation increased with the decrease in T (6-7 hours at -1 degree C and 2.5-3 hours at +18 degrees C). At phase of increased thermogenesis during arousal heart temperature exceeded rectal one on 10-12 degrees C and heart rate run up to 360-420 beat/min i.e. 2-3 time higher than in active state. The decrease in T stimulated the increase in HP up to 3.8 in winter and 5.3 beat/min/degree C in summer. The highest values of Q10 for HP were revealed at the beginning of hibernation (15-20) and at the beginning of arousal (6-7), in other periods Q10 was similar to the normal biological values (2-2.5). Thus, at the beginning of transitional periods changes of HP were determined mainly by endogenic mechanisms that inhibited myocardium at the beginning of hibernation and activated in arousal. Some mechanisms of coordination between activities of heart and other systems of organism are considered. The features of hit exchange providing the hibernation in wide range of T are discussed.     

Developmental changes in heart and muscle phosphofructokinase isozymes

Phosphofructokinase isozymes of fetal, neonatal, and adult rat heart and skeletal muscle were characterized by DEAE-cellulose chromatography, agarose gel electrophoresis, and immunodiffusion with specific antisera. The results of these studies indicate that in skeletal muscle and heart the levels of the major liver phosphofructokinase isozyme (PFK-L2) and the muscle phosphofructokinase isozyme (PFK-M) are dependent on the developmental status of the rat. For example, PFK-L2 and PFK-M are present in fetal and early neonatal skeletal muscle; whereas in adult skeletal muscle, only PFK-M is detectable. By DEAE- cellulose chromatography, PFK-L2 activity was estimated to be 2.4 units/g (41% of total phosphofructokinase activity) in fetal muscle, very low and not resolved from PFK-M in 7-day neonatal muscle, and not detectable in adult muscle. Further, PFK-M activity was found to be 3.4 units/g (59% of total phosphofructokinase activity), 10 units/g, and 31.6 units/g in fetal, 7-day neonatal, and adult skeletal muscle, respectively. The developmental changes of heart phosphofructokinase isozymes differ considerably from that of the skeletal muscle phosphofructokinase isozymes. In fetal heart, PFK-L2 is the major phosphofructokinase isozyme (5.6 units/g), constituting 67% of total phosphofructokinase activity. Further, in fetal heart another phosphofructokinase isozyme (33% of total phosphofructokinase activity) was found by DEAE-cellulose chromatography which is different from PFK-M and PFK-L2. In 7-day neonatal and adult heart, PFK-M and PFK-L2 are the only detectable phosphofructokinase isozymes. Varying from 5.6 units/g (44% of total) in 7-day neonatal to 5.9 units/g (40% of total) in adult heart, PFK-L2 activity remains fairly constant. Also, PFK-M is very low in fetal heart but increases within 1 week postpartum to 5.5 units/g (50% of total activity) and to 8.9 units/g (60% of total activity) in adult heart.     

Diurnal changes in net uptake rate of nitrate are associated with changes in estimated export of carbohydrates to roots

The rate of NO3- uptake by soybean (Glycine max [L.] Merrill) roots generally declines during the night in association with progressive depletion of the nonstructural carbohydrate pool in the shoot as well as the concentration of carbohydrates in roots. To determine if NO3- uptake rate changes in response to variations in translocation rate of carbohydrates from shoot to roots per se or to carbohydrate status of the roots, the night period was interrupted with a low light level from incandescent lamps to alter the diurnal pattern of NO3- uptake by roots and export of carbohydrate from shoots of nonnodulated soybean. Depletion of NO3- from replenished, complete nutrient solutions containing 1 mM NO3- was measured by ion chromatography and rates of NO3- uptake were calculated. Changes in export of carbohydrates from shoot to roots during intervals of the night period were calculated as the differences between rates of disappearance in contents of nonstructural carbohydrates and their estimated rates of utilization in shoot respiration and growth. A positive, significant correlation occurred between changes in calculated rates of carbohydrate export from shoots and NO3- uptake rates. Conversely, there was no significant correlation between concentrations of nonstructural carbohydrates in roots and NO3- uptake rates. These results support the hypothesis that carbohydrate flux from shoot to roots has a direct role in regulation of nitrogen uptake by the whole plant.     

Physiological effects of cocaine in the squirrel monkey.

Doses of cocaine that have previously been shown to have behavioral effects produced dose-related increases in arterial blood pressure, heart rate and core temperature in unanesthetized squirrel monkeys ($\text{Saimiri}$$\text{sciureus}$). The pressor effect was immediate, but heart rate increased more gradually after cocaine injection. The onset of hyperthermia was substantially delayed. The squirrel monkey may be a good animal model of the physiological concomitants of cocaine abuse in humans.     

Cholesterol metabolism in rhesus monkey, squirrel monkey, and baboon

The metabolism of cholesterol was studied in baboons, rhesus monkeys, and squirrel monkeys while they were being fed either a low fat, low cholesterol (basal) diet or the basal diet supplemented with saturated fat and cholesterol (atherogenic diet). When the diet was changed from basal to atherogenic, the mean total serum cholesterol concentration increased from 70 to 180 mg/dl in the baboon, from 168 to 283 mg/dl in the squirrel monkey, and from 144 to 608 mg/dl in the rhesus monkey. In animals fed the atherogenic diet, the percentage of dietary cholesterol absorbed was greatest in the rhesus monkey and least in the baboon. The fraction of the total body pool of cholesterol that was derived from the diet was greatest in the squirrel monkey and least in the baboon. The turnover of the body pool of cholesterol was several times faster in the squirrel monkey than in the baboon or the rhesus monkey when either dict was fed. The mean total fecal excretion of endogenous cholesterol and bile acid increased in all species on transition to the atherogenic diet; however, the relative contributions of the neutral and acidic fractions to the increase in total excretion differed among species. The difference in percentage of dietary cholesterol absorbed may, in part, account for the large differences in serum cholesterol during the atherogenic diet period. Comparison with other published results indicates that of these species cholesterol metabolism in the baboon is most like that in the human.     

Comparison of antigenicity of serum immunoglobulin G among human, cynomolgus monkey, African green monkey and squirrel monkey

Antigenicity of IgG was compared among human, the cynomolgus monkey, the African green monkey and the squirrel monkey by the quantitative precipitation test using purified IgG of and rabbit anti-IgG serum to each species. Clear cross-antigenicity was observed between the cynomolgus monkey and the African green monkey and less clear cross-antigenicity between human and the cynomolgus monkey or the African green monkey. The cross-antigenicity observed between the squirrel monkey and the other three species examined was evidently weak.