Physiological profiles of episodic progesterone release during the midluteal phase of the human menstrual cycle: analysis of circadian and ultradian rhythms, discrete pulse properties, and correlations with simultaneous luteinizing hormone release

To define the physiological relationships between episodic progesterone and LH release, we measured serum progesterone and LH concentrations in blood sampled at 10-min intervals for 24 h in seven young women in the midluteal phase of the menstrual cycle. The resultant time series were assessed further by Fourier transformation, Cluster analysis, and cross-correlation analysis with autoregressive modeling. These techniques permitted an examination of circadian rhythms, discrete (ultradian) pulse properties, and simultaneous or lagged correlations between progesterone and LH release. We found the following. 1) Both serum LH and progesterone concentrations had significant circadian periodicities, with similar acrophases (times of maximal nyctohemeral values). LH and progesterone also manifested multiple ultradian rhythms of similar periodicities (range, 48-241 min). 2) Discrete serum progesterone peaks occurred at a mean interpulse interval of 118 +/- 12 (+/- SE) min, had durations of 92 +/- 12 min, and had incremental amplitudes of 4.3 +/- 0.9 ng/mL (14 +/- 3 nmol/L). The frequency and duration characteristics of the progesterone and LH peaks were not significantly different, but progesterone fractional peak amplitudes were one quarter those of LH pulses. 3) Fractional progesterone peak amplitudes in the seven women correlated inversely (r = -0.811) with 24-h mean LH concentrations, suggesting a negative feedback relationship between progesterone and LH release. 4) LH and progesterone interpulse intervals both exhibited significant nyctohemeral variations, with diurnal amplitudes of 73 +/- 12 min for LH and 43 +/- 8.9 min for progesterone (P less than 0.01). 5) Significant positive cross-correlations existed in all seven women between serum LH and progesterone concentrations considered simultaneously and at progesterone time lags of 10-50 min. By autoregressive modeling, the later (20-50 min) cross-correlations could be accounted for by sustained autocorrelations in the individual progesterone and LH time series and significant cross-correlations between LH and simultaneous progesterone concentrations and between LH and 10-min lagged progesterone concentrations. We conclude that progesterone release occurs in a periodic (circadian and ultradian) fashion as well as in a discrete (episodic or pulsatile) mode. Moreover, both positive and negative feedback relationships operate to coordinate LH and progesterone secretion in the midluteal phase of the human menstrual cycle.     

The effect of growth hormone on the insulin-like growth factor system during fasting

The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity.     

The Intentional Differences: A Qualitative Study of the Views and Experiences of Non-peer Mental Health Providers on Working Together with Peer Support Colleagues in Mental Health

Community Mental Health Journal - The study reports the results of a qualitative study on the views and experiences of non-peer mental health providers on working together with peer colleagues in...     

Protective measures for patients with advanced cancer during the Sars-CoV-2 pandemic: Quo vadis?

Clinical & Experimental Metastasis - Cancer patients represent a vulnerable cohort during the Sars-CoV-2 pandemic. Oncological societies have generated a plethora of recommendations, but...     

Intranasal ketorolac,diagnosis, and desensitization for aspirin-exacerbated respiratory disease

BackgroundIntranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization.ObjectiveWe conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD.MethodsPatients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013. Participants selected either one of the following desensitization protocols: intranasal ketorolac 1 day before oral ASA (group 1, combined) or ketorolac challenge with greater than 2 weeks elapsing until oral ASA (group 2, washout). All patients were on a leukotriene-modifying drug (montelukast) for at least 1 week before the challenge.ResultsA total of 20 patients were enrolled: 13 in group 1 and 7 in group 2. No significant differences were seen for baseline symptom scores or forced expiratory volume in 1 second. Group 1 exhibited significant increases for the threshold dose of ASA (P = .009), the likelihood of having silent ASA desensitization (P = .01), and decreased reaction severity to oral ASA (P = .04). There were no significant differences in reaction forced expiratory volume in 1 second, the incidence of extrapulmonary symptoms, limited nasoocular reactions, rescue treatment requirements, or time to symptom resolution. There was 100% concordance between reactions to intranasal ketorolac and oral ASA for group 2, supporting its use as a diagnostic test for AERD.ConclusionIntranasal ketorolac is a useful diagnostic test and adjunct within the combined ketorolac/ASA protocol to achieve effective, efficient, and perhaps safer desensitization to ASA for patients with AERD.     

Analyzing age-specific genetic effects on human extreme age survival in cohort-based longitudinal studies

The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies. Our approach is characterized by non-parametric analysis of late age survival to capture the observed pattern of mortality deceleration and frailty modeling to account for individual heterogeneity in unobserved frailty. The method is applied to ApoE genotype data in the Danish 1905 birth cohort to estimate effect of the e4 allele. Our results revealed an age-specific relative risk of the allele that increases nonlinearly with age and non-proportional patterns in hazard of death for carriers and non-carriers of the allele, suggesting that the e4 mutation preserves its deleterious effect that progressively affect human survival even at extreme ages.     

Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products

BACKGROUND: Animal studies of arthritis have suggested that bisphosphonates may have chondroprotective abilities. OBJECTIVE: To evaluate the effect of bisphosphonate treatment on cartilage degradation. METHODS: Type II collagen is almost exclusively localised in cartilage, where it is the major structural component of the tissue. Hence fragments derived from this protein should represent a specific index for cartilage degradation. The urinary concentration of collagen type II C-telopeptide degradation products (CTX-II) was measured by a new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum concentration of collagen type I C-telopeptide degradation products (CTX-I), a marker of bone degradation, was also measured by ELISA. PARTICIPANTS: Two groups were studied. The alendronate group included 63 healthy postmenopausal women aged 45-54 randomly allocated to receive three years' treatment with 1 mg, 5 mg, 10 mg, or 20 mg alendronate daily or placebo. In the third year the women receiving 20 mg were switched to placebo. The ibandronate group included 119 women at least 10 years after the menopause aged <75 randomly allocated to receive 12 months' treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or placebo followed by 12 months without treatment. RESULTS: 20 mg of alendronate and 2.5 and 5 mg of ibandronate treatment produced significant decreases in urinary CTX-II to about 50% of baseline. The level reached after three months of treatment remained practically constant during the following 12-36 treatment months. When treatment was withdrawn CTX-II values returned towards baseline. Serum CTX-I also decreased rapidly within three months, but to a level of about 30% of baseline. CONCLUSIONS: The urinary excretion of CTX-II, a new marker of cartilage degradation, decreases significantly in response to bisphosphonate. This suggests that bisphosphonates may have chondroprotective effects in humans. By measurement of CTX-II it should be possible to monitor the effects of drugs that potentially inhibit cartilage destruction.