Recombinant human prolactin for the treatment of lactation insufficiency

Context Lactation insufficiency has many aetiologies including complete or relative prolactin deficiency. Exogenous prolactin may increase breast milk volume in this subset. We hypothesized that recombinant human prolactin (r‐hPRL) would increase milk volume in mothers with prolactin deficiency and mothers of preterm infants with lactation insufficiency. Design Study 1: R‐hPRL was administered in an open‐label trial to mothers with prolactin deficiency. Study 2: R‐hPRL was administered in a randomized, double‐blind, placebo‐controlled trial to mothers with lactation insufficiency that developed while pumping breast milk for their preterm infants. Patients Study 1: Mothers with prolactin deficiency (n = 5). Study 2: Mothers of premature infants exclusively pumping breast milk (n = 11). Design Study 1: R‐hPRL (60 μg/kg) was administered subcutaneously every 12 h for 28 days. Study 2: Mothers of preterm infants were randomized to receive r‐hPRL (60 μg/kg), placebo or r‐hPRL alternating with placebo every 12 h for 7 days. Measurements Change in milk volume. Results Study 1: Peak prolactin (27·9 ± 17·3 to 194·6 ± 19·5 μg/l; P < 0·003) and milk volume (3·4 ± 1·6 to 66·1 ± 8·3 ml/day; P < 0·001) increased with r‐hPRL administration. Study 2: Peak prolactin increased in mothers treated with r‐hPRL every 12 h (n = 3; 79·3 ± 55·4 to 271·3 ± 36·7 μg/l; P < 0·05) and daily (101·4 ± 61·5 vs 178·9 ± 45·9 μg/l; P < 0·04), but milk volume increased only in the group treated with r‐hPRL every 12 h (53·5 ± 48·5 to 235·0 ± 135·7 ml/day; P < 0·02). Conclusion Twice daily r‐hPRL increases milk volume in mothers with prolactin deficiency and in preterm mothers with lactation insufficiency.     

Characterization of the estrous cycle and assessment of reproductive status in Matschie's tree kangaroo (Dendrolagus matschiei) with fecal progestin profiles

The population of Matschie’s tree kangaroos (Dendrolagus matschiei) held in North American zoos has declined to critically low numbers, and information on the reproductive biology of tree kangaroos is limited. The objectives of this study were to (1) characterize the temporal features of the estrous cycle through the measurement of fecal progesterone metabolite (i.e., progestin) concentrations and (2) determine the reproductive status of female tree kangaroos in the captive population of North America through the identification of estrous cyclicity. Fecal pellets and observations of estrous behaviors were collected from 16 captive female tree kangaroos. Fecal pellets were sampled and extracted with methanol, and progestin concentrations were quantified using a radioimmunoassay (RIA) for progesterone and its metabolites. A progestin profile was obtained for each female by plotting fecal progestin concentrations for every third day over a 120-day period. Profiles for 12 of 16 females showed evidence of estrous cyclicity (P < 0.01). The mean length of the estrous cycle was estimated at 58.9 ± 2.4 days (n = 11). Progestin concentrations were low during the first 15-20 days of the luteal phase and remained elevated above baseline only during the last 30.2 ± 3.2 days of the luteal phase, which averaged 46.6 ± 2.5 days in duration. The progestin profile observed in the estrous cycle of Matschie’s tree kangaroos in this study is very similar to that seen in the non-pregnant cycle of several other species in the family Macropodidae.     

HUMAN α-LACTALBUMIN AND HORMONAL FACTORS IN PREGNANCY AND LACTATION

Serum α-lactalbumin was monitored throughout pregnancy in twelve women and in a separate group of nineteen women during the first 3 months postpartum. During pregnancy α-lactalbumin rose significantly until the mid trimester (P < 0·001). From then until term, concentrations remained stable. Concentrations during labour were significantly higher (P < 0·01) than those seen at term, α-lactalbumin, 17β-oestradiol and progesterone concentrations behaved similarly during the first week of the puerperium in both lactating (n= 10) and non-lactating (n= 9) subjects. A large surge of α-lactalbumin closely followed the clearance of high circulating concentrations of sex steroids in both groups. Prolactin concentrations were significantly greater (P < 0·02) in lactating subjects by the third postpartum day. By the third postpartum week α-lactalbumin concentrations in lactating subjects had stabilized at labour levels in a milieu of high prolactin levels and depressed production on 17β-oestradiol and progesterone. Conversely, in non-lactating subjects α-lactalbumin concentrations fell, as did prolactin, coincidental with a rise in 17β-oestradiol, progesterone concentrations remaining barely detectable. The apparent control mechanisms for human α-lactalbumin secretion and thus, lactation, are discussed in the light of the data presented.     

Effects of estradiol on concentrations of gonadotropin-releasing hormone receptor messenger ribonucleic acid following removal of progesterone

To test the hypothesis that low levels of estradiol are sufficient to increase concentrations of GnRH receptor mRNA in the absence of progesterone, ewes were ovariectomized and immediately treated with estradiol implants for 12 h to achieve circulating concentrations of estradiol typical of the early (n=5) or late (n=4) follicular phase. Five additional ewes underwent lutectomy, and control ewes were untreated. Treatment of ewes with 1/2 or 1 estradiol implant increased concentrations of estradiol in serum to 3.0 ± 0.8 pg/ml or 6.3 ± 0.3 pg/ml, respectively, and concentrations of estradiol in lutectomized ewes (2.4 ± 0.5 pg/ml) were intermediate. Ovariectomy did not alter concentrations of GnRH receptor mRNA or numbers of GnRH receptors. Treatment of ewes with 1 estradiol implant increased concentrations of GnRH receptor mRNA and numbers of GnRH receptors. In ewes treated with 1/2 estradiol implant, concentrations of GnRH receptor mRNA were intermediate between controls and ewes treated with 1 estradiol implant, and numbers of GnRH receptors were greater than controls. Lutectomy increased concentrations of GnRH receptor mRNA but did not affect numbers of GnRH receptors. We conclude that estradiol stimulates expression of the GnRH receptor gene and numbers of GnRH receptors in the absence of progesterone. However, effects of estradiol on expression of the GnRH receptor gene were clearly evident only when concentrations of estradiol were elevated to levels typical of the late follicular phase.     

Relationships between tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and hematopoietic activity in healthy adults

To investigate the relationship between hematopoiesis and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we measured soluble TRAIL concentrations, reticulocytes, hemograms, and anthropometric variables in 156 healthy subjects. Serum TRAIL concentrations were analyzed by an enzyme immunoassay. Serum ferritin, thyroid hormone, total cholesterol, creatinine, and blood glucose levels were determined. There were no significant differences in blood cell counts and biochemical parameters between the subjects with TRAIL less than 63.5 pg/ml and TRAIL at least 63.5 pg/ml, nor between those with TRAIL at most 47.5 pg/ml (20th percentile) and TRAIL 80.9 pg/ml (80th percentile). However, hemoglobin, mean corpuscular hemoglobin (MCH), and MCH concentration (MCHC) averaged 15.6±0.8 g/dl, 31.9±1.1 pg, and 34.5±0.9 g/dl in the subjects with TRAIL at most 47.5 pg/ml, which were significantly above the values in those with TRAIL at least 80.9 pg/ml (14.7±0.9 g/dl, 30.4±1.3 pg, and 33.2±1.2 g/dl, P<0.05, respectively). Serum TRAIL levels were significantly higher in the subjects with decreased MCH than in those with elevated MCH. Soluble TRAIL concentrations were significantly correlated with hemoglobin (r=–0.25, P<0.05), MCH (r=–0.32, P<0.05), and MCHC (r=–0.29, P<0.05), but not correlated with leukocyte differentials and platelet counts. In conclusion, soluble TRAIL does not seem to influence leukocyte and platelet production but has an important relationship to erythropoiesis in healthy adults.     

Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis

Summary Interleukin-6 (IL-6) was detected at low levels in plasma [0.014±0.006 ng/ml (mean ± SEM] and in high amounts in synovial fluid [SF; 2.6±2.2 ng/ml (mean ± SEM)] of patients with rheumatoid arthritis. No correlation of IL-6 levels in plasma or SF with the ESR (n=15) or with histological parameters of acute local synovitis (n=10) was observed. In contrast, SF IL-6 was positively correlated with histological characteristics of chronic synovitis (n=10; P0.01) and elevated plasma IgG concentrations (n=15; P0.05). In vitro concentrations of IL-6 comparable to those detected in SF increased the production of both IgG and IgM by synovial membrane mononuclear cells. The present results contribute to the view that high local IL-6 concentrations in SF promote chronic synovitis in RA.     

Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised,multicentre studies

Ravulizumab, a novel long-acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non-inferior to eculizumab for all efficacy outcomes in two randomised, open-label, phase 3 trials in C5 inhibitor-naïve (Study 301) and eculizumab-experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre-specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, n = 246; Study 302, n = 195). Ravulizumab PK parameters were determined using non-compartmental analysis. Serum free C5 was quantified with a Gyros-based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand-binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2·3 to 2·8 and 2·3 to 2·6 h in studies 301 and 302, respectively. Ravulizumab steady-state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) post hoc terminal elimination half-life was 49·7 (8·9) days. Serum free C5 concentrations <0·5 µg/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations <0·5 µg/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every-2-weeks in patients with PNH.     

Increased Plasma Levels of Corticosterone and Prolactin and Decreased T3 and T4 Levels in Short-Term Prehepatic Portal Hypertension in Rats

Corticosterone, T₃, T₄, and prolactin serum concentrations at 24 hr (N = 10), 15 days (N = 10), and 45 days (N = 10) of postoperative (postop) evolution were assayed to study the neuroendocrine response to portal hypertension. A triple stenosing ligature of the portal vein was used as the surgical technique of portal hypertension. This technique does not produce mortality and causes a decrease in the serum concentrations of T₃ (0.043 ± 0.009 vs 0.55 ± 0.08 ng/ml) and T₄ (3.93 ± 0.55 vs 4.65 ± 0.67 g/ml) and an increase in those of prolactin (28.61 ± 20.20 vs 12.84 ± 3.96 ng/ml) and corticosterone (397.50 ± 64.17 vs 311.53 ± 57.41 ng/ml) at 45 days postop. The T₃, T₄, prolactin, and corticosterone alterations are associated with a persistent increase of TNF- and NO, whose serum concentrations at 45 days postop are, respectively, 1838.33 ± 247.07 vs 48.89 ± 8.75 pg/ml and 0.43 ± 0.13 vs 0.19 ± 0.01 mmol/ml. TNF- and NO could mediate these hormonal alterations in the evolution of short-term portal hypertension in the rat; thus they are involved in the systemic neuroendocrine response that is induced by this injury.     

High serum folates and the simplification of red cell folate analysis

Recent substantial increases in clinical blood folate concentrations are noted. Since red cell folates (RCF) are calculated from whole blood folates (WBF) by subtraction of the endogenous serum folate (SF) component, the reporting of clinical RCF results may be delayed because an ever increasing proportion (15%) of diagnostic SF levels are high (> 20 ng/ml) and need a repeat analysis. We evaluated ‘plasma replacement’ as a simple preanalytical procedure in which endogenous blood plasma is removed from red cells by washing and substituted with ‘low‐folate’ plasma (serum) as an alternative conjugase (gamma‐glutamyl carboxypeptidase) source for folate polyglutamate hydrolysis. Washed and conventional RCF assays compared well after both manual (n=115, r=0.98, y=1x + 1.26) and automated washing of red cells (n=170, r=0.96, y=0.96x – 0.73 ng/ml) and were not significantly different. The interassay reproducibility of folate results from washed blood samples was good (CV=< 6%). This novel ‘plasma replacement’ step halves the cost of a valid RCF assay by eliminating the need for endogenous SF analysis, and it expedites the reporting of clinical results.     

Aldosterone escape during blockade of the renin–angiotensin–aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate

Aims/hypothesis It has been suggested that aldosterone plays a role in the initiation and progression of renal disease independently of arterial blood pressure and plasma angiotensin II levels. We evaluated the influence of plasma aldosterone levels on progression of diabetic nephropathy during long-term blockade of the renin–angiotensin–aldosterone system.Methods A total of 63 hypertensive patients with type 1 diabetes and diabetic nephropathy were treated with losartan, 100 mg once daily, for a mean follow-up period of 35 months. Plasma aldosterone, GFR, albuminuria and 24-h blood pressure were determined at baseline and at regular intervals during the study.Results Patients were divided according to their increasing or decreasing levels of plasma aldosterone during long-term losartan treatment in an escape group (n=26) and a non-escape group (n=37). In the escape group, aldosterone levels increased from (geometric mean [95% CI]) 57 pg/ml (43–76 pg/ml) at 2 months, to 102 pg/ml (78–134 pg/ml) at the end of the study (p<0.01). The corresponding levels in the non-escape group were 83 pg/ml (69–102 pg/ml) and 49 pg/ml (40–60 pg/ml; p<0.01). The median rate of decline in GFR was 5.0 ml·min^–1·year^–1 (range 0.4–15.9 ml·min^–1·year^–1) in the escape group, compared with 2.4 ml·min^–1·year^–1 (–1.6 to 11.0 ml·min^–1·year^–1) in the non-escape group (p<0.005). The increase in plasma aldosterone correlated with the rate of decline in GFR (r²=0.19, p<0.001), corresponding to a decline in GFR of 1.5 ml·min^–1·year^–1 for every two-fold increase in plasma aldosterone. Pre-treatment and treatment values of plasma aldosterone were not related to albuminuria or to changes in albuminuria during the study.Conclusions/interpretation Our data suggest that aldosterone escape during long-term blockade of the renin–angiotensin–aldosterone system is associated with an enhanced decline in GFR in patients with type 1 diabetes and diabetic nephropathy.Conflict of interest. Hans-Henrik Parving received honoraria or consulting fees from Merck, AstraZeneca, BMS, Sanofi-Synthelabo and Pfizer, and grant/research support from Merck and Sanofi-Synthelabo.     

Serum prolactin concentrations in the captive female African elephant (Loxodonta africana): potential effects of season and steroid hormone interactions

Research was conducted to determine whether seasonal changes in prolactin secretion occur in nonpregnant female African elephants and to examine potential functional interrelationships between secretion of prolactin, cortisol, and progesterone. Weekly blood samples were taken for 18 months from four female African elephants and the sera were analyzed by RIA for progesterone, cortisol, and prolactin concentrations. There was no significant effect of season on serum concentrations of prolactin. Estrous cycles averaged 14 weeks in length and were composed of a 9-week luteal phase and a 5-week follicular phase (based on progesterone concentrations consistently >200 and <200 pg/ml, respectively). Estrous cycle synchronicity was evident between pairs of elephants. Serum concentrations of prolactin (3.91 +/- 0.69 ng/ml; range: 0.84-15.8 ng/ml) were significantly lower during the luteal, compared with the follicular, phase (P < 0.0001; t test) and were positively correlated with serum concentrations of cortisol (r = 0.14; P < 0.05). Mean (+/-SE) serum concentration of cortisol was 5.7 +/- 1.3 ng/ml (range: 1.4-19.3 ng/ml), and concentrations of this adrenal steroid were negatively correlated with progesterone concentrations (r = -0.15; P < 0.01). Increased serum concentrations of prolactin detected during the follicular phase suggest that this hormone may be regulated by ovarian estrogens and may play a role in modulating ovarian function in the elephant.     

Regulated plasma levels of colony-stimulating factors,interleukin-6 and interleukin-10 in patients with acute leukaemia and non-Hodgkin's lymphoma undergoing cytoreductive chemotherapy

Endogenous plasma levels of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-10 were measured in a total of 70 patients undergoing cytoreductive chemotherapy for treatment of acute leukaemia or non-Hodgkin’s lymphomas. The diagnoses were acute myeloid leukaemia (AML; n = 30), acute lymphoblastic leukaemia (ALL; n = 6), non-Hodgkin’s lymphomas (NHL; n = 11) and other malignant haematological disorders including myelodysplastic syndromes (n = 23). After chemotherapy, plasma G-CSF was elevated (mean 5.6 ng/ml; range 1.2–10 ng/ml), and was inversely correlated with white blood cell counts (WBC) (r = ?0.7, P < 0.001). Occurrence of fever (T>38.0°C) during severe myelosuppression (WBC<1 × 10⁹/l) was associated with an additional increase of G-CSF levels (P < 0.001). Plasma IL-6 correlated significantly with fever (range <1 to 1100 pg/ml, mean 130 pg/ml; r = 0.5, P < 0.001) but revealed only a weak association with WBC or platelet counts. In patients treated with recombinant G-CSF (n = 9), an association between IL-6 and fever was still observed after chemotherapy. During the nonfebrile status (total n = 242; AML n = 124), IL-6 levels remained <9 pg/ml in 90% of cases, whereas G-CSF increased with leucopenia (r = ?0.72; P < 0.001). In contrast, endogenous GM-CSF remained normal and IL-10 showed only a slight increase (21% of samples; maximum 22 pg/ml) in severe leucopenia. In particular, IL-10 levels did not correlate with G-CSF or IL-6 levels. We conclude that systemic release of G-CSF and IL-6 is obviously not abrogated by cytoreductive chemotherapy in acute leukaemia and NHL and may add to the therapeutic efficacy of recombinant cytokines. Also, plasma levels of G-, GM-CSF or IL-6 appear to be regulated by separate mechanisms.     

In patients with idiopathic venous thrombosis, interleukin-10 is decreased and related to endothelial dysfunction

The aim of this study was to evaluate the levels of anti-inflammatory interleukin-10 and pro-inflammatory cytokines and their relationship to endothelial function in patients with idiopathic venous thrombosis. Forty-nine eligible patients of both sexes with idiopathic venous thrombosis and 48 matched control subjects were studied. Levels of inflammatory markers were determined. Endothelial function was evaluated by ultrasound measurement of the flow mediated dilatation (FMD) of the brachial artery. Compared to the control group, patients with idiopathic venous thrombosis had significantly lower levels of interleukin-10 1.81 pg/ml (1.53–2.21) versus 2.71 pg/ml (1.84–3.65), p < 0.001. Patients also had increased levels of pro-inflammatory cytokines: interleukin-6 2.37 pg/ml (1.59–4.09) versus 2.03 pg/ml (1.49–2.59), p = 0.025, interleukin-8 3.53 pg/ml (2.94–5.30) versus 2.25 pg/ml (1.77–2.90), p < 0.001. Furthermore, decreased FMD was observed in patients: 5.0% (3.9–6.9) versus 12.7% (10.8–15.6), p < 0.001. FMD was related to levels of interleukin-10 (r = 0.33, p = 0.001) and was inversely related to pro-inflammatory cytokines interleukin-6 (r = −0.34, p = 0.001) and interleukin-8 (r = −0.43, p < 0.001). Patients with idiopathic venous thrombosis have decreased levels of IL-10 and increased levels of pro-inflammatory cytokines. This imbalance indicates that in the stable phase of the disease, patients have an increased systemic inflammatory response. This inflammatory response could be the consequence of the disease, but most probably is involved in the pathogenesis of venous thrombosis.     

Urinary vasodilator and vasoconstrictor angiotensins during menstrual cycle, pregnancy, and lactation

Since normal human pregnancy is characterized by normotension in the face of an increased renin-angiotensin-aldosterone system (RAAS), we evaluated the temporal pattern of urinary excretion of a novel vasodilator within this system, angiotensin-(1–7) (Ang-[1–7]), during the menstrual cycle, pregnancy, and lactation. The urinary profiles of Ang I, Ang II, human chorionic gonadotropin, 17β-estradiol, and progesterone were also determined. During the menstrual cycle, urinary Ang-(1–7) and Ang II remained stable (mean cycle value: 94.6±11.3 and 11.4±1.1 pmol/g of creatinine, respectively) in nine females. In 10 normal pregnant women, urinary Ang-(1–7) and Ang II increased throughout gestation, averaging 1499.8±310 and 224.4±58 pmol/g of creatinine, respectively (p<0.05) at wk 35 and falling during lactation to 394.0±95 and 65.7±20 pmol/g of creatinine (p<0.05), respectively. The Ang-(1–7)/Ang II ratio was unchanged in the different reproductive periods. During the menstrual cycle, Ang II and Ang-(1–7) correlated with 17β-estradiol and progesterone using multivariate analysis (r=0.31, p<0.001) and r=0.28, p<0.02, respectively). During gestation, 17β-estradiol and progesterone correlated with urinary Ang-(1–7) (r=0.48, p<0.001 and r=0.47, p<0.001, respectively) and Ang II (r=0.24, p<0.03 and r=0.25, p<0.03, respectively); by multiple regression, only Ang-(1–7) correlated with both steroids (r=0.49, p<0.001). The progressive rise of Ang-(1–7) throughout gestation, probably modulated by estrogen and progesterone, suggests a physiologic counterregulation within the RAAS.     

Periovulatory enhancement of spontaneous prolactin secretion in normal women

The role of endogenous estrogen in the regulation of prolactin secretion in man is controversial. To study this question further, spontaneous prolactin patterns were determined over 5 hr in 10 normal women during the early follicular and again during the periovulatory phases of the menstrual cycle. Steroid determinations revealed significant elevations in mean ±1 SE E₁ (113 ± 20 versus 55 ± 5 pg/ml), E₂ (144 ± 47 versus 48 ± 9 pg/ml), and 17-OHP (1,301 ± 266 versus 639 ± 46 pg/ml) during the periovulatory compared to the early follicular phase period. Each subject demonstrated increased mean plasma prolactin concentration during the higher estrogen state. Mean prolactin concentration (calculated from the individual mean values of samples obtained at 15 min intervals for 5 hr) during the midcycle study period was 10.7 ± 1.0 ng/ml compared to the early follicular phase period of 8.1 ± 1.0 ng/ml (p < 0.0005). The mean percent increment in plasma prolactin during the periovulatory period was 39% with a range of 9 to 117%. There was no correlation between mean prolactin and serum E₁, E₂, P, or 17-OHP levels during either study period. However, the incremental change in prolactin showed a positive correlation with the incremental increase in E₂ (correlation coefficient, r = 0.66, p < 0.05). In contrast, no significant correlation was present between mean incremental change in prolactin and E₁, P, or 17-OHP. These data suggest that enhanced cyclic estrogen secretion during the periovulatory phase of the menstrual cycle is associated with significantly increased serum prolactin concentrations.     

Levels of IL-32 in Serum,Induced Sputum Supernatant,and Bronchial Lavage Fluid of Patients with Chronic Obstructive Pulmonary Disease

Interleukin-32 (IL-32) is a newly described cytokine which is expected to have an important role in autoimmune disorders. It was shown that chronic obstructive pulmonary disease (COPD) has a component of autoimmunity, though the role of IL-32 in its pathogenesis is not known. The aim of this study was to estimate IL-32 concentrations in serum, induced sputum (IS) supernatant and bronchoalveolar lavage (BAL) fluid from patients with COPD, and to compare asthma patients with and healthy subjects. Outpatients with COPD (63.7 ± 8.4 years, n = 51), asthma (58.3 ± 12.4 years, n = 31), and healthy subjects (59.8 ± 8.2 years, n = 9) were studied. The levels of IL-32 in serum, BAL fluid, and IS supernatant samples were analyzed by ELISA. Concentrations of IL-32 were higher in all the studied materials from patients with COPD (BAL 22.46 ± 2.48 pg/ml, IS 19.66 ± 1.69 pg/ml, serum 26.77 ± 2.56 pg/ml) in comparison with patients with asthma (BAL 6.25 ± 1.08 pg/ml, IS 5.82 ± 1.15 pg/ml, serum 6.09 ± 1.16 pg/ml, p < 0.05 respectively) as well as healthy subjects (BAL 4.21 ± 1.13 pg/ml, IS 3.59 ± 0.66 pg/ml, serum 4.63 ± 1.03 pg/ml, p < 0.05 respectively). Moreover, the level of IL-32 was higher in COPD smokers than in COPD ex-smokers in investigated respiratory tissue compartments and serum, and correlated with smoking history. Increased level of IL-32 in serum, IS supernatant, and BAL fluid from patients with COPD in comparison with asthma patients and healthy subjects suggest that IL-32 may play an important role in the pathogenesis of COPD, which depends on the smoking history.     

Variations in serum androgens,estrogens, progestins,gonadotropins and prolactin levels in male rats from prepubertal to advanced age

The concentrations of blood serum steroids from 12 to 450 days old male rats were determined by radioimmunoassay. Testosterone (T) was low (270 pg to < 1 ng/ml) until day 42; adult levels (3–4 ng/ml) were attained by day 62 and declined gradually with advanced age. 5α -dihydrotestosterone (5α-DHT) did not change markedly (90–160 pg/ml) from prepubertal to advanced age. Except for a small peak on day 22, androstenedione (Δ⁴ A) levels ranged between 400–500 pg/ml in the adult but declined in older males. Progesterone (Δ⁴ P) rose steadily to a mean of 5.46 ng/ml at 52 days of age and dropped thereafter. High levels of estrone (268 ± 38 pg/ml) and estradiol- 17β (2.76 ± 0.28 ng/ml) in 12 days old males are in contrast to the low estrogens (20–35 pg/ml) in adult animals. Both T/5α-DHT and total T/estrogen ratios were low before puberty, increased in adults and decreased towards old age. The interplay between gonadotropin and prolactin, which exhibited reciprocal changes in the regulation of steroid production by the gonads with age, are discussed.     

A Heterologous Assay for Measuring Prolactin in Pituitary Extracts and Plasma from Australian Flying Foxes (GenusPteropus)

A sensitive heterologous assay was developed to measure prolactin-like activity inPteropus alecto, P. poliocephalus,andP. scapulatus,Australian flying foxes. Adapted from an established radioimmunoassay for rabbit PRL, it utilises the well-characterised, polyclonal antiserum 33/9 (guinea pig anti-human prolactin). In the assay, pituitary extracts fromP. alecto, P. poliocephalus,andP. scapulatusdiluted in parallel with ovine prolactin standards, although absolute levels estimated were low. Its usefulness for investigating the role of prolactin in reproduction and seasonality in flying foxes was tested. In a survey of pituitary extracts collected from both sexes of all three species, prolactin was higher in females than in males (P < 0.001). In the few specimens from juveniles, mean prolactin levels in pituitary and plasma were similar to those of adults. Plasma and pituitary samples both contained higher concentrations of prolactin during late pregnancy (P. scapulatus,plasmaP < 0.01; pituitaryP < 0.01) and lactation (P. poliocephalus,plasmaP < 0.005; pituitaryP < 0.05) in mature females. Plasma prolactin increased at about the time of parturition, but returned to nonpregnant levels rapidly if lactation was not established. In lactating females, plasma prolactin was suppressed by temporary removal of the sucking young, and was slow to recover after the young was returned to the nipple. Pharmacological responses were tested in pregnantP. poliocephalus:plasma prolactin was low following bromocriptine administration and elevated following domperidone. Prolactin is concluded to play significant roles in the reproductive physiology of female flying foxes and, as in other species, is under dopaminergic regulation.     

Degradation of 125I-labelled prolactin in the rabbit: effect of nephrectomy and prolactin infusion

The concentrations of progesterone and oestradiol-17 beta in the maternal plasma of Bennett's wallaby, Macropus rufogriseus rufogriseus, were measured daily throughout gestation after reactivation of the diapausing corpus luteum by removal of the suckling pouch young (RPY). Progesterone increased from mean concentrations of 382-424 pmol/l (120-133 pg/ml) during lactation to reach peak concentrations of 908 +/- 172 (S.E.M.) pmol/l (285 +/- 54 pg/ml) (n = 8) 4 days after RPY and 971 +/- 220 and 971 +/- 229 pmol/l (305 +/- 69 and 305 +/- 72 pg/ml) (n = 7) 24 and 25 days after RPY respectively. The mean gestation length (RPY to birth) was 26.8 +/- 0.6 (S.D.) days (n = 6, range 25.75-27.50 days). Immediately after birth the plasma progesterone concentration declined to 299 +/- 51 (S.E.M.) pmol/l (94 +/- 16 pg/ml) (n = 6). Oestradiol-17 beta increased from mean concentrations of 291-553 pmol/l (80-152 pg/ml) during lactation to reach a peak concentration of 967 +/- 331 pmol/l (266 +/- 91 pg/ml) (n = 9) 1 day after RPY. The concentration declined from 7 days after RPY and fluctuated between mean concentrations of 273 and 480 pmol/l before reaching a minimum of 207 +/- 69 pmol/l (57 +/- 19 pg/ml) (n = 6) 19 days after RPY. A transient increase to 542 +/- 207 pmol/l (n = 7) occurred at 22 days after RPY. Plasma concentrations declined to a low of 156 +/- 55 pmol/l (43 +/- 15 pg/ml) (n = 6) 5 days after parturition. The mean concentration of plasma 13,14-dihydro-15-oxo-prostaglandin F2 alpha was less than 2.8 nmol/l (1 ng/ml) for all samples from 13 days after RPY until 4 days after parturition. The results suggest that oestradiol-17 beta may be important in the early stages of blastocyst reactivation to synergize with progesterone in stimulating uterine secretions. 13,14-Dihydro-15-oxo-prostaglandin F2 alpha is unlikely to be involved in the birth process and any luteolytic effect is likely to be from a local production of PGF2 alpha.