Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome

BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17α activity are both features of the polycystic ovary syndrome. P450c17α, which is involved in androgen biosynthesis, has both 17α-hydroxylase and 17,20-lyase activities. Increased activity of this enzyme results in exaggerated conversion of progesterone to 17α-hydroxyprogesterone in response to stimulation by gonadotropin. We hypothesized that hyperinsulinemia stimulates ovarian P450c17α activity. METHODS We measured serum steroid concentrations during fasting and the response of serum 17α-hydroxyprogesterone to leuprolide, a gonadotropin-releasing hormone agonist, and performed oral glucose-tolerance tests before and after oral administration of either metformin (500 mg three times daily) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome. RESULTS In the 11 women given metformin, the mean (±SE) area under the serum insulin curve after oral glucose administration decreased from 9303±1603 to 4982±911 μU per milliliter per minute (56±10 to 30±6 nmol per liter per minute) (P = 0.004). This decrease was associated with a reduction in the basal serum 17α-hydroxyprogesterone concentration from 135±21 to 66±7 ng per deciliter (4.1±0.6 to 2.0±0.2 nmol per liter) (P = 0.01) and a reduction in the leuprolide-stimulated peak serum 17α-hydroxyprogesterone concentration from 455±54 to 281±52 ng per deciliter (13.7±1.6 to 8.5±1.6 nmol per liter) (P = 0.01). The serum 17α-hydroxyprogesterone values increased slightly in the placebo group. In the metformin group, the basal serum luteinizing hormone concentration decreased from 8.5±2.2 to 2.8±0.5 mlU per milliliter (P = 0.01), the serum free testosterone concentration decreased from 0.34±0.07 to 0.19±0.05 ng per deciliter (12±3 to 7±2 pmol per liter) (P = 0.009), and the serum sex hormone–binding globulin concentration increased from 0.8±0.2 to 2.3±0.6 μg per deciliter (29±7 to 80±21 nmol per liter) (P CONCLUSIONS In obese women with the polycystic ovary syndrome, decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17α activity and ameliorates hyperandrogenism

Minority youth and social transformation in Australia: Identities, belonging and cultural capital

© 2014 by the authors; licensee Cogitatio (Lisbon, Portugal). Increasingly minority youth, especially from Muslim backgrounds, have been seen in Australian public policy and the media as potentially disruptive and transgressive. In some European societies similar young people have been portrayed as living in parallel and disconnected social spaces, self-segregated from interaction with the wider community. Yet Australian ethnic minority youth do not fulfil either of these stereotypes. Rather, despite their often regular experiences of racism or discrimination, they continue to assert a strong identification with and belonging to Australian society, albeit the society that marginalizes and denigrates their cultural capital. In particular it is the neighbourhood and the locality that provides the bridge between their home cultures and the broader world, contributing to a range of positive aspirations and fluid identities

Treatment of patients with distant metastases from phyllodes tumor of the breast

BACKGROUND: Here, the treatment methods and results of patients with phyllodes tumor of the breast (PT) with distant metastases at a single institution are presented. METHODS: A retrospective analysis was performed on a group of 295 patients with PT treated from 1952 to 2010. RESULTS: Distant metastases developed in 37 (12.5 %) patients; 3/160 (1.9 %) patients had benign PT, 6/36 (16.7 %) were considered borderline, and 28/99 (28.3 %) had malignant PT. Most frequently, the metastases were located in the lungs; 28 (75.7 %), bone 7 (18.9 %), brain 4 (10.8 %), and liver 2 (5.4 %). Metastases occurred on overage 21 months (2–57) after surgery. Patients with lung metastases were generally treated with monochemotherapy or polychemotherapy. In one patient Testosterone and in two patients resection of metastases combined with Doxorubicin were used. Patients with bones or brain metastases were treated with palliative radiotherapy only or combined with Doxorubicin. The mean survival (MS) from diagnosis of distant metastases (DM) was 7 months (2–17). The longest mean survival in patients with bones metastases was 11.8 months, the worst survival was for patients with brain metastases—2.8 months. Hormone therapy appeared to have low efficacy (MS: 2 months) as well as monochemotherapy (MS: 3–5 months). Improved MS was obtained using Doxorubicin (7 months) and Doxorubicin with Cisplatin, Cyclophosphamide, or Ifosfamide (9 months). CONCLUSION: The prognosis of patients with DM from PT is poor. The role of surgery and irradiation of such patients is very limited. There appears to be no role for the use of hormone therapy. This study showed that polychemotherapy with Doxorubicin and Ifosfamide suggest that it might be more effective than once thought

The Role of Magmatism in Hydrocarbon Generation in Sedimented Rifts: a Nd Isotope Perspective from Mid-Cretaceous Methane-Seep Deposits of the Basque-Cantabrian Basin, Spain

Studies on the involvement of intrusive magmatism in hydrocarbon generation within sedimentary basins have gained momentum owing to increasing appraisal of the role that such processes may play in controlling global carbon cycle perturbations, and the exploration potential of the volcanic sedimentary basins. Nevertheless, for many areas the causal link between the intrusions and surrounding hydrocarbon systems remains disputed, encouraging a search for methods that could aid in identifying different hydrocarbon sources. Here, we have performed a multi-proxy geochemical study of the middle Cretaceous methane-seep deposits of the Basque-Cantabrian Basin, an early-stage, peri-cratonic rift marking the Mesozoic opening of the Bay of Biscay. Infilled by a thick sedimentary succession intruded by shallow-level igneous bodies, the basin shares analogies with modern young, sedimented rifts that sustain hydrocarbon seepage. We have applied a novel approach that uses the Nd isotope composition of the seep deposits to constrain the relationship between hydrocarbon seepage and igneous activity, and to explore the general potential of Nd isotopes to trace magmatic-influenced fluids in volcanic sedimentary basins. The Nd isotope data have been combined with rare earth element analyses and carbon and oxygen isotope measurements, providing broad insight into the former composition of the seeping fluids. For three out of four investigated seeps, the Nd isotope ratios observed in authigenic seep carbonates include signatures markedly more radiogenic than that reconstructed for background seawater-derived pore waters. The level of this Nd-143-enrichment varies both between and within individual deposits, reflecting spatial and temporal differences in fluid composition typical of seep-related environments. The radiogenic Nd isotope signals provide evidence of subseafloor interactions between the seeping fluids and mafic igneous materials, supporting the model of an igneous control on the mid-Cretaceous methane expulsion in the Basque-Cantabrian Basin. The thermogenic origin of the methane is in accord with the moderately negative delta C-13 values and paragenetic successions observed in the studied seep carbonates. For a single deposit, its relatively unradiogenic Nd isotope composition can be attributed to the smallest size and shallowest emplacement depth of the underlying intrusion, likely resulting in a short-lived character and limited hydrocarbon-generation potential of the associated contact metamorphism. The study demonstrates that Nd isotope analyses of seep carbonates offer a tool in disentangling methane fluxes from different organic matter alteration pathways for the numerous, both fossil and modern sedimented rifts for which the involvement of various methane sources remains insufficiently understood.This work was supported by the National Science Centre, Poland (grant No. 2016/23/D/ST10/00444; to MJ) , and the Eusko Jaurlaritza (Ikerketa Taldeak IT930-16) and the Spanish State Research Agency (project PID2019-105670GB-I00/AEI/10.13039/501100011033; both to LMA

Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome

ABSTRACT Background Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene. Methods We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome. Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo. Serum progesterone was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on any of these days. Results Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study. Among the 21 women given metformin plus clomiphene, the mean (±SE) area under the serum insulin curve after oral glucose administration decreased from 6745±2021 to 3479±455 µU per milliliter per minute (40.5±12.1 to 20.9±2.7 nmol per liter per minute, P=0.03), but it did not change significantly in the 25 women given placebo plus clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus clomiphene ovulated (mean peak serum progesterone concentration, 23.8±3.4 ng per milliliter [7.6±10.9 nmol per liter]). Two of the 25 women (8 percent) who received placebo plus clomiphene ovulated (P\u3c0.001). Overall, 31 of the 35 women (89 percent) treated with metformin ovulated spontaneously or in response to clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo. Conclusions The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin. (N Engl J Med 1998;338:1876-80.

Air Gauge Characteristics Linearity Improvement

This paper discusses calibration uncertainty and linearity issues of the typical back-pressure air gauge. In this sort of air gauge, the correlation between the measured dimension (represented by the slot width) and the air pressure in the measuring chamber is used in a proportional range. However, when high linearity is required (e.g., nonlinearity less than 1%), the measuring range should be shortened. In the proposed method, based on knowledge of the static characteristics of air gauges, the measuring range is kept unchanged but the nonlinearity is decreased. The static characteristics may be separated into two sections, each of them approximated with a different linear function. As a result, the nonlinearity is reduced from 5% down to 1% and even below

Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome

BACKGROUND Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a d-chiro-inositol–containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of d-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. METHODS We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of d-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation. RESULTS In the 22 women given d-chiro-inositol, the mean (±SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417±11,572 to 5158±6714 μU per milliliter per minute (81±69 to 31±40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1±0.8 to 0.5±0.5 ng per deciliter (38±28 to 17±17 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women\u27s diastolic and systolic blood pressure decreased by 4 mm Hg (Pchiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P\u3c0.001). CONCLUSIONS d-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations

74 Ocena skuteczności leczenia przerzutów odległych u chorych na miejscowo wyleczonego raka szyjki macicy

Cel pracyOcena skuteczności leczenia przerzutów odległych u chorych na miejscowo wyleczonego raka szyjki macicy.MetodykaRetrospektywna analiza materiału obejmującego 113 chorych na miejscowo wyleczonego RSM, u których wystąpiły przerzuty odległe. Wszystkie chore badanej grupy były leczone w Krakowskim Oddziale Centrum Onkologii (COOK) w latach 1986–1992. Oceniono wpływ leczenia chirurgicznego na przeżycie chorych oraz efekt paliatywny tego leczenia.WynikiNajczęstszą lokalizacją pierwszego lub pierwszych przerzutów były płuca (37 chorych), kości (26 chorych) i wątroba (20 chorych); ponadto stwierdzono przerzuty do mózgu (11 chorych), obwodowych węzłów chłonnych (11 chorych) i skóry (8 chorych). U [[mml:math altimg="si1.gif"]][[mml:mrow]][[mml:mstyle scriptlevel="1"]][[mml:mfrac bevelled="true"]][[mml:mn]]3[[/mml:mn]][[mml:mn]]4[[/mml:mn]][[/mml:mfrac]][[/mml:mstyle]][[/mml:mrow]][[/mml:math]] chorych stwierdzono przerzuty pojedyncze, u 1/4 mnogie. W ciągu pierwszego roku po leczeniu miejscowym, przerzuty odległe wystąpiły u 42,5% chorych, w ciągu 3 lat u ponad [[mml:math altimg="si1.gif"]][[mml:mrow]][[mml:mstyle scriptlevel="1"]][[mml:mfrac bevelled="true"]][[mml:mn]]3[[/mml:mn]][[mml:mn]]4[[/mml:mn]][[/mml:mfrac]][[/mml:mstyle]][[/mml:mrow]][[/mml:math]] chorych; średni czas wystąpienia przerzutów wynosił 23 miesiące. Spośród 113 chorych badanej grupy, leczenie przyczynowe przerzutów odległych podjęto jedynie u 48 tzn. 42,5% pacjentek; u 3 chorych zastosowano leczenie operacyjne (metastazektomia pojedynczych przerzutów do płuc), u 20 wyłącznie teleradioterapię, u kolejnych 20 wyłącznie chemioterapię, u 5 skojarzenie chemioradioterapii. Od momentu wystąpienia przerzutów odlegfych,odległych, 12 miesięcy przeżyło jedynie 15% chorych badanej grupy, a 24 miesiące 4% chorych.Wnioski1.Zarówno telaradioterapia jak i chemioterapia oparta na cysplatynie z 5-fluorouracylem lub karboplatynie, nie miały statystycznie znamiennego wpływu na przeżycia chorych badanej grupy.2.Telaradioterapia jest skuteczną metodą łagodzenia dolegliwości u chorych z przerzutami RSM do kości, obwodowych węzłów chłonnych i skóry