Sirkka-Liisa Karonen

Ischemic pain nonsegmentally produces a predominant reduction of pain and thermal sensitivity in man: A selective role for endogenous opioids

Ischemic pain was produced by a blood pressure cuff placed to the arm of healthy human subjects for 15 min which produced a mean pain score of 59% (visual analogue scale). Ischemia induced a significant dental pain threshold elevation (mean 67%) and 2 mg of naloxone did not reduce it. Thermal sensitivity of the upper lip had a tendency to reduction during ischemia and 2 mg of naloxone reduced this effect. Tactile thresholds in the forehead or in the contralateral arm were not markedly elevated. Neither ACTH nor prolactin level in the plasma was related to the dental pain threshold elevation during ischemia. The findings of the present study suggest that ischemic pain nonsegmentally produces a predominant inhibition of responses to thin afferents. Endogenous opioids may markedly contribute to the reduction of thermal sensitivity induced by ischemia, but their contribution to dental pain threshold elevations seems to be less important. Stress or other adenohypophyseal mechanisms involving the release of ACTH or prolactin do not explain the effects of ischemia found in the present study.

Modification of dental pain and cutaneous thermal sensitivity by physical exercise in man

The effect of physical exercise on dental pain thresholds, the release of pituitary stress hormones and thermal sensitivity of skin was tested in healthy human subjects. Different levels of exercise (100-300 W) at different pedal frequencies were produced by a cycle ergometer. Thermal limen (the interval between warm and cool thresholds) determined from glabrous hand, hairy forearm and leg was used as a parameter of thermal sensitivity. In all subjects the heart rate and blood pressure were increased with increasing work load. Dental pain thresholds were elevated at high work loads with a concomitant activation of pituitary stress hormone (especially growth hormone) release. Thermal limens at all 3 sites were increased work load, too, independent of the pedal frequency. The increase of thermal limen was most marked in the leg and least in the glabrous hand. The results indicate that physical exercise produces a non-segmental, load-dependent decrease of pain and thermal sensitivity with a concomitant activation of pituitary stress mechanisms. The magnitude of modification varies with skin region. Activation of inhibitory mechanisms at spinal levels via muscle and proprioceptive afferents, in a way suggested by the gate control theory of pain mechanisms, seems to have only a minor, if any, contribution to the present findings, since a higher pedal frequency did not produce a more marked decrease of sensitivity.

Low plasma testosterone values in men during hangover

Abstract Plasma testosterone, estradiol, estrone and luteinizing hormone concentrations were measured by radioimmunoassay in healthy volunteers who after fasting for 10 h consumed 1.5 g ethanol/kg body wt. Of this group five suffered from severe hangover while another five had essentially no hangover. Ten to twenty hours after drinking, the testosterone concentrations were significantly decreased in all subjects, but in the 5 subjects with severe hangover the decrease was more pronounced. Estradiol values decreased during the hangover period, but were normal at the time of acute intoxication, whereas estrone values, in the few cases determined, showed a tendency to increase during acute intoxication. A compensatory increase in the plasma concentration of luteinizing hormone was found in all subjects.

Transient Hypoparathyroidism during Acute Alcohol Intoxication

BACKGROUND Persons with chronic alcoholism frequently have hypocalcemia, hypomagnesemia, and osteoporosis. The short-term effects of alcohol ingestion on calcium and magnesium metabolism are poorly understood, however. METHODS We measured serum calcium, magnesium, and phosphate concentrations in 17 normal men and 7 normal women before and at intervals up to 16 hours after the ingestion of 1.2 to 1.5 g of alcohol per kilogram of body weight over a 3-hour period (doses sufficient to cause acute intoxication). Urinary excretion of calcium, magnesium, and phosphate and serum calciotropic hormone levels were measured in 16 of these subjects. As a control, the same measurements were made after the ingestion of fruit juice instead of alcohol. RESULTS The mean (+/- SE) peak blood alcohol level in the men was 37.5 +/- 1.6 mmol per liter, and in the women it was 38.0 +/- 3.2 mmol per liter. In the men the mean serum parathyroid hormone concentration decreased from 16.1 +/- 2.1 to 6.8 +/- 0.9 ng per liter at the end of the three-hour drinking period. The value at this time was 30 percent of that at the end of the three-hour session during which the men drank fruit juice (P = 0.004). The serum concentration of ionized calcium reached a nadir eight hours after the beginning of alcohol administration (decreasing from 1.18 +/- 0.01 to 1.15 +/- 0.01 mmol per liter; P less than 0.001 as compared with values during the fruit-juice study), and urinary excretion of calcium increased from 0.34 +/- 0.08 to 0.36 +/- 0.08 mmol per hour (P less than 0.01 as compared with values during the fruit-juice study). Serum parathyroid hormone levels exceeded base-line values during the last 4 hours of the 16-hour study period; this increase was accompanied by a decrease in the urinary excretion of calcium. Both serum levels of magnesium (in the first 6 hours) and urinary levels (in the first 12 hours) increased after the ingestion of alcohol. In the women, serum parathyroid hormone levels decreased from 29.2 +/- 2.8 to 17.3 +/- 2.6 ng per liter two hours after the administration of alcohol was begun (P less than 0.001) and increased above base-line values during the last four hours of the study period. The serum concentration of ionized calcium decreased from 1.20 +/- 0.01 to 1.16 +/- 0.01 mmol per liter, reaching a nadir 8 to 12 hours after alcohol administration was begun (P less than 0.001). CONCLUSIONS Short-term alcohol administration causes transitory hypoparathyroidism. This decline in the secretion of parathyroid hormone accounts at least in part for the transient hypocalcemia, hypercalciuria, and hypermagnesuria that follow alcohol ingestion.

Pathogenesis and Prevention of the Dawn Phenomenon in Diabetic Patients Treated with CSII

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 ± 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 ± 0.4 mmol/L to 6.1 ± 0.7 mmol/L (P < 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 ± 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 ± 0.03 mg/kg/ min, P < 0.02). When the patients were restudied after the infusion rate was increased by 49 ± 7%, Ra fell to 1.75 ± 0.03 mg/kg/min (P < 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P / 0.05) than in eight healthy control subjects, in whom Ra (1.66 ± 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 ± 0.5 mU/L) and increased infusion rate (11.3 ± 0.4 mU/L), and higher than those of the control subjects (5.2 ± 0.2 mU/L, P < 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61; P < 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects. In conclusion: (1) A dawn phenomenon is associated with an excessive rate of glucose production, rather than impaired utilization; (2) this may be explained, at least in part, by elevated counterregulatory hormone levels; and (3) a step-up in the overnight insulin delivery reduces hepatic glucose production and so prevents the dawn phenomenon.

Bedtime Insulin for Suppression of Overnight Free–Fatty Acid, Blood Glucose, and Glucose Production in NIDDM

We studied the clinical effectiveness and mechanism underlying the glucose-lowering effect of evening insulin therapy. Nocturnal profiles of blood glucose, plasma free fatty acid (FFA), glycerol, and lactate and overnight glucose kinetics ([3-3H] glucose infusion) were measured in 15 non-insulin-dependent diabetic (NIDDM) patients with a relative body weight of 128 ± 4% who were poorly controlled with oral therapy alone. The patients were studied before and 2 wk and 3 mo after bedtime insulin (23 ± 3 IU) was given in addition to oral therapy. An early-morning rise in blood glucose (>31 mg/dl = 1.5 mM) was present in two-thirds of the patients and was associated with an overnight rise in plasma FFA and an increase in glucose production (Ra) during the early-morning hours (change 0.42 ± 0.10 mg · kg−1 · min−1 P < .05, between 0300 and 0800). The overnight mean levels of blood glucose, plasma FFA, and serum insulin averaged 212 ± 9 vs. 137 ± 11 vs. 133 ± 11 mg/dl (P < .001), 674 ± 61 vs. 491 ± 57 vs. 484 ± 36 μM (P < 0.01) and 12.7 ± 1.6 vs. 18.1 ± 2.2 vs. 20.7 ± 2.4 μU/ (P < .01) before and 2 wk and 3 mo after the combination therapy. The decrements in overnight glucose and FFA levels after 2 wk of bedtime insulin therapy were closely correlated (r = .86, P < .001). The nocturnal profile of plasma lactate was similar before and during bedtime insulin therapy. The overnight mean glucose Ra fell significantly after insulin administration (2.31 ± 0.13 vs. 1.83 ± 0.09 vs. 1.83 ± 0.10 mg · kg−1 min−1 P < .01, respectively). There was a positive correlation between the overnight mean values of Ra and the plasma FFA concentration (r = .58, P < .001). These data raise the possibility the improvement in overall glycemic control by the administration of evening insulin is related to the suppression of overnight plasma FFA concentrations and to a consequent reduction in overnight glucose production.

Effects of 3 weeks' moderate alcohol intake on bone and mineral metabolism in normal men

To study the effects of prolonged moderate alcohol intake on bone and mineral metabolism, 60 g/day of ethanol was administered to 10 healthy male volunteers during 3 weeks. The drinking period was preceded and followed by an abstinence period of 3 weeks. The serum level of osteocalcin decreased by 30% towards the end of the alcohol period (P less than 0.01), recovering by 25% after the termination of drinking (P less than 0.01). The serum level of intact parathyroid hormone increased to the end of the drinking period (P less than 0.05). After stopping drinking it came back to baseline (P less than 0.05) within a week. The serum levels of 25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3, the serum and urinary levels of calcium, and the intestinal absorption of calcium measured by stable strontium remained practically unchanged throughout the whole observation period. We conclude that prolonged moderate alcohol intake impairs osteoblastic function, leading to lowered serum levels of osteocalcin, but it does not derange vitamin D metabolism.

Changes in Leptin Concentration during the Early Postnatal Period: Adjustment to Extrauterine Life?

There are substantial alterations in fuel homeostasis immediately after birth. Leptin is a putative regulator of energy metabolism. Consequently, the aim of this study was to examine whether there are changes in circulating leptin concentrations during the early postnatal period. Umbilical cord mixed blood samples were taken at delivery, and a venous blood sample was obtained at 3 d of age from 38 healthy newborn infants (20 male, 18 female; gestational age 36.3 to 41.9 wk) for analysis of leptin concentration with radioimmunoassay. Cord plasma leptin concentration was 9.7 ± 5.2 µg/L (mean ± SD), with no gender difference between male (8.6 ± 4.6 µg/L) and female (10.9 ± 5.6 µg/L) infants. In male newborns, cord plasma leptin concentration correlated with arm circumference (r = 0.48, p < 0.05), and in female newborns with body mass index (r = 0.62, p < 0.01), thickness of the s.c. fat (r = 0.54, p < 0.05), and arm circumference (r = 0.72, p < 0.01). By the third postnatal day, plasma leptin decreased similarly in male (to 1.8 ± 0.4 µg/L, p < 0.001) and female (to 2.3 ± 0.8 µg/L, p < 0.001) infants, when there was a significant gender difference in leptin levels (p = 0.01). At 3 d of age, plasma leptin correlated with weight (r = 0.49, p < 0.05) and arm circumference (r = 0.49, p < 0.05) in female but not in male newborns. In conclusion, 1) circulating leptin already correlates with adiposity at birth in female but not in male newborn infants and 2) leptin decreases markedly in both genders by the third postnatal day, and the gender difference with higher leptin levels in females develops by that time. Thus, the postnatal decrease in plasma leptin concentration may be a physiologically feasible adaptation to profound alterations in fuel homeostasis during the first days of extrauterine life.

The aminoterminal propeptide of type I procollagen: Evaluation of a commercial radioimmunoassay kit and values in healthy subjects

OBJECTIVES Evaluation of the performance of a radioimmunoassay kit for measuring serum concentrations of the aminoterminal extension peptide of human type I procollagen, S-PINP. DESIGN AND METHODS S-PINP concentrations in 229 healthy subjects, 140 females, aged 3.8-81 years, and 89 males, aged 0.9-71 years, were measured with the kit. Because PINP and PICP (the carboxy-terminal propeptide of type I procollagen) are formed in equimolar concentrations, we also calculated the PICP/PINP ratio and compared the S-PINP values to those of S-PICP, which have been shown to correlate with bone formulation rate. RESULTS The sensitivity of the assay was 2.3 micrograms/L, the spiking recovery ranged from 95.5 to 100.3%, the dilution recovery from 79.3 to 103.1%. The intra-assay imprecision was 2.3 to 3.5% (CV), the interassay imprecision within one reagent lot 2.5-5.2% and, between several reagent lots, 2.7 to 6.1% (CV). S-PINP in females over 20 years old ranged from 12 to 90 micrograms/L (x = 39.7, SD = 14.7), in males over 25 years old, from 22 to 89 micrograms/L (x = 49.9, SD = 15.8); the PICP/PINP ratio ranged from 1.5 to 5.2 and from 1.8 to 4.9, respectively. In females under 20 years old, S-PINP ranged from 52 to 820 micrograms/L, in males aged 25 years or younger from 35 to 1404 micrograms/L; the PICP/PINP ratio was 0.44-2.3 and 0.38-2.8. In females under 20 years and males under 25 years, there was a significant negative correlation between S-PINP and age: r = -0.70, p < 0.001 for females, r = -0.52, p = 0.004 for males. In different groups of healthy subjects, the correlation of S-PINP and S-PICP was significant (r = 0.67-0.86, p < 0.001). CONCLUSION The assay performance is good. The significant positive relationship between S-PINP and S-PICP suggests that S-PINP also reflects bone formation rate. Because the clearance of PINP is probably less sensitive to hormonal changes, PINP may prove to be superior to PICP as a marker of bone formation.

Dental analgesia produced by non-painful low-frequency stimulation is not influenced by stress or reversed by naloxone

Abstract The dental pain threshold elevation produced by non‐painful, low‐frequency transcutaneous electrical nerve stimulation (TENS) in healthy humans was not reduced by the administration of 0.8 mg of naloxone i.v. Neither ACTH, prolactin nor growth hormone (GH) release were related to the pain threshold elevations. The present study indicates that the dental pain threshold elevation during non‐painful, low‐frequency TENS is not based on the same opioid‐dependent mechanisms as the dental pain threshold elevation during acupuncture or the clinical analgesia during low‐frequency TENS. Stress or other adenohypophyseal mechanisms involving ACTH, prolactin or GH do not explain the analgesia induced by non‐painful, low‐frequency TENS.