BACKGROUND:Natural killer cells (NKC) are a major component of the innate immune response to HCV, mediating their effects through TRAIL and IFN-γ. However, their function is diminished in chronic HCV patients (HCVp). Prolactin is an immunomodulatory hormone capable of activating NKC.OBJECTIVE:The study aims to explore if hyperprolactinemia can activate NKC in HCVp.METHODS:We treated twelve chronic HCVp (confidence level =95%, power =80%) for 15 days with Levosulpiride plus Cimetidine to induce mild hyperprolactinemia. Before and after treatment, we determined TRAIL and NKG2D expression on peripheral blood NKC, along with cytokine profiles, viral loads and liver function. We also evaluated in vitro effects of prolactin and/or IL-2 on NKC TRAIL or NKG2D expression and IFN-γ levels on cultured blood mononuclear cells from 8 HCVp and 7 healthy controls.RESULTS:The treatment induced mild hyperprolactinemia and increased TRAIL expression on NKC as well as the secretion of IL-1ra, IL-2, PDGF and IFN-γ. Viral loads decreased in six HCVp. IL-2 and TRAIL together explained the viral load decrease. In vitro, prolactin plus IL-2 synergized to increase TRAIL and NKG2D expression on NKC from HCVp but not in controls.CONCLUSION:Levosulpiride/Cimetidine treatment induced mild hyperprolactinaemia that was associated with NKC activation and Th1-type cytokine profile. Also, an increase in TRAIL and IL-2 was associated with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.

Evidence supporting the role of PRL as a Th1-type cytokine and its potential therapeutic implications in human immunodeficiency virus (HIV) infection, graft-versus-host disease (GVHD), chronic hepatitis C (CHC) and preeclampsia is reviewed. In patients with HIV infection, dopaminergic adaptive mechanisms maintain PRL at a high but physiological concentration, which stimulates CD4(+) T lymphocyte proliferation and increases viral apoptosis attempting to survive. In patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation complicated by chronic GVHD, the dopaminergic adaptive mechanisms tend to decrease the high normal serum PRL concentrations. On the contrary, in transplantations complicated by acute GVHD, donors with a Th1 cytokine profile may be prone to induce acute GVHD in their recipients, but a mild sustained rise in PRL concentrations after transplantation in these patients may reduce the severity of the disease. In patients with CHC, mild, drug-induced hyperprolactinemia is associated with increased peripheral lymphocytes and natural killer cell cytotoxicity that induces apoptosis in the infected hepatocytes. In early pregnancy, endogenous low-molecular-weight PRL (14-16 kDa) may act as a Th1-cytokine participating in the faulty trophoblastic invasion of the placenta in women with subsequent severe preeclampsia. In conclusion, PRL may participate as an important immunoregulatory factor in the pathophysiology of HIV infection, GVHD, CHC and preeclampsia through its Th1-type cytokine-like actions.

Objective: To explore, the prevalence of gestational diabetes mellitus (GDM), defined by the previous criteria of the American Diabetes Association (ADA), as well as the criteria suggested by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), in an unselected group of urban Mexican pregnant women and to analyze the frequency of large for gestational age (LGA) newborns in this same group of women with use of both diagnostic criteria.Methods: A cross-sectional study included 803 consecutive Mexican urban women with a singleton pregnancy, without concomitant diseases and no prior history of GDM, who underwent a 2-step screening protocol for diagnosis of GDM at admission to prenatal care.Results: The ADA criteria identified 83 women (10.3%) whereas the IADPSG criteria diagnosed 242 women (30.1%) having GDM (P = .0001). Fasting glucose concentrations during the 100-g 3-hour oral glucose tolerance test were abnormal in 116 women (14.4%) and in 160 women (19.9%) on the basis of ADA and IADPSG criteria, respectively (P = .004). The frequency of LGA newborns was 7.4% based on IADPSG criteria and 6.0% based on ADA criteria - no significant difference (P = .64).Conclusion: With use of the IADPSG criteria, the prevalence of GDM increased almost 3-fold in comparison with that for the ADA criteria. Nevertheless, no significant difference was found in the prevalence of LGA newborns. (Endocr Pract. 2012;18:146-151)

Objective: To study the incidence of gestational diabetes mellitus (GDM) in Mexican women with a history of infertility and polycystic ovary syndrome (PCOS) compared with women without PCOS matched by age, pregestational body mass index (BMI), and parity.Design: Historic cohort study.Setting: Level three medical institution.Patient(s): Group 1 (n = 52), women with a history of infertility and PCOS, and group 2 (n = 52), women without PCOS. Inclusion criteria were singleton pregnancy with <= 13 weeks of gestation. Exclusion criteria were pregestational diabetes mellitus and/or concomitant diseases.Intervention(s): Diagnosis of GDM was based on a 3-hour, 100-g oral glucose tolerance test (GTT) performed during the second trimester.Main Outcome Measure(s): Incidence and relative risk (RR) for GDM.Result(s): The incidence of GDM was 26.9% and 9.6% for groups 1 and 2, respectively (RR = 2.8; 95% confidence interval 1.08-7.2). No other between-group differences were observed in the incidence of miscarriage, preterm birth, premature rupture of membranes, preeclampsia, stillbirth, fetal malformations, or small or large for gestational age newborns.Conclusion(s): Pregnant Mexican women with a history of infertility and PCOS are at increased risk for developing GDM. This risk should be considered beginning early in the second trimester for a timely intervention and to improve the maternal-fetal prognosis. (Fertil Steril (R) 2012;97:1467-71. (C) 2012 by American Society for Reproductive Medicine.)

Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Background/Aims: To compare the gestational weight gain and adverse perinatal outcomes in urban Mexican women with prepregnancy overweight or obesity, under an early intensive obstetric and nutrition program versus women with prepregnancy normal weight. Methods: A cohort of 546 pregnant women with prepregnancy normal weight (n = 201, NW), overweight (n = 171, OW) or obesity (n = 174, OB), ≤13 weeks of gestation and a singleton pregnancy. OW and OB groups were under early intensive obstetric and nutritional care and NW group was under routine prenatal care. Miscarriage, hypertensive disorders, premature rupture of membranes, preterm birth, stillbirth, gestational diabetes mellitus (GDM) and large- or small-for-gestational-age newborns, were compared between groups. Results: Weight gain was smaller in OB than in OW or NW (mean ± SD): 6.1 ± 4.4, 9.5 ± 5.1, 10.3 ± 5.4 kg, respectively (p < 0.001). OB women had the highest frequency of GDM (p < 0.001), lack of spontaneous labor (p < 0.001) and preeclampsia (p < 0.001), but no other between-group differences existed. Conclusion: Early intensive medical-nutrition prenatal care and adequate gestational weight gain may contribute to decreasing most maternal and newborn adverse outcomes associated with prepregnancy overweight or obesity.

The acute effect of sleep deprivation on the pituitary-testis axis was evaluated in 13 healthy men. To study such association, the circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), Androstenedione (A), Testosterone (T), Dihydro-testosterone (DHT) and Estradiol (E2) were measured along with Cortisol (C) before and after sleep deprivation. Morning (8:00 AM) venous blood samples were obtained prior and after a continuous restless period of 24 hr and the values were analyzed by the paired Student's t test. There was a significant and parallel decrease of each androgen and E2 but not of FSH, L.H. PRL, or C, associated with the acute sleep deprivation.Key Words: Sleep disturbanceAndrogensCortisolGonadotropinsProlactin

Insulin resistance (IR) increases during late pregnancy enhancing the risk of impaired glucose intolerance (IGT) or gestational diabetes mellitus (GDM). Overweight and obese women are at risk for IGT or GDM. Diet is used to treat of GDM, but the relationship between maternal diet and IR in pregnancy is not clear. Objective: To identify dietary factors that influence IR and post glucose load insulin sensitivity (IS) in overweight/obese Mexican women during mid and late gestation.MethodsThirty‐seven overweight Mexican women (BMI: 28.7+4.2) were studied. Nutrition counseling was given at baseline (20 wks gestation). Dietary intakes were estimated from three 24‐hr recalls done between 21 and 28 wk gestation. A 100g oral glucose tolerance test (OGTT) was performed at 28wk. The Homeostasis Model Assessment (HOMA‐IR), the Matsuda/DeFronzo Insulin Sensitivity Index and the insulin area under the curve (AUC) were determined.ResultsDietary polyunsaturated fat (PUFA) intake explained 12% of the variability in HOMA‐IR at 28 wk (p<0.05), and the % energy from protein explained 12% of the variability in the insulin AUC (0.05); none of the dietary variables were related to IS.ConclusionIn this population, HOMA‐IR declined by 4% for each gram of PUFAs consumed per 1000 kcals/day suggesting that pregnant women at risk for IR and GDM should be encouraged to increase their PUFA intake. Partially supported by UC Mexus

Impaired glucose tolerance is associated with adverse pregnancy outcomes. Early detection would allow implementing interventions to reduce progression to Gestational Diabetes Mellitus (GDM). Hispanic women are a risk group for GDM. The objective was to identify biochemical, anthropometric and dietary factors that predict insulin resistance, Homeostasis Model Assessment‐Insulin Resistance (HOMA‐IR), at 16‐20 or 26‐30 wk gestation in 109 pregnant women living in Mexico City. Maternal health history, anthropometry and dietary intakes were measured at 16‐20 wk . Dietary intakes were assessed using a validated food frequency questionnaire. Fasting insulin, glucose, adiponectin, and leptin concentrations were measured at 16‐20 and 26‐30 wk. HOMA‐IR and leptin increased (HOMA‐IR: 2.6±1.5 to 3.1±1.9 and leptin: 25.5 ± 12 to 27.3 ± 14 ng/mL) while adiponectin decreased between time points (12.1 ± 5 to 11.5 ± 5 ug/mL). At 16‐20 wks, stepwise multiple regression analysis showed that maternal weight, fasting leptin and adiponectin concentrations were the strongest predictors of HOMA‐IR. At 26‐30 wks, sugar intake, maternal weight and subscapular skinfold thicknesses best predicted HOMA‐IR. Maternal weight was the only variable predicting HOMA‐IR at both mid and late pregnancy. These results support programs targeting overweight and obese women for weight control to reduce the risk of GDM. Funded by UCMexus.

BACKGROUND The aim of the study was to determine whether a predictive value for the diagnosis of gestational diabetes mellitus (GDM) could be established using different glucose screening test thresholds in Mexican urban pregnant women. MATERIAL/METHODS A group of 635 pregnant women (12-33 weeks of gestation) with serum glucose screening values of > or = 7.2 mmol (> or = 130 mg/dl) were evaluated with a 100-g 3-h oral glucose tolerance test (OGTT). The positive predictive values (PPVs) for serum glucose screening values of > or = 7.2 mmol to > or = 11.1 mmol (> or = 130 to > or = 200 mg/dl), age, and pregestational BMI were calculated. RESULTS Of the women, 304 (47.8%) had a normal OGTT, 126 (19.8%) had impaired glucose tolerance, and 205 (32.3%) had GDM. A serum glucose screening value of > or = 9.4 mmol (> or = 170 mg/dl) had a positive predictive value (PPV) of 0.85 and the relative risk for GDM was 6.62 (95%CI: 4.40-9.97, p=0.001). Omission of the 3-h value during OGTT yielded a sensitivity of 91.2% (187/205). CONCLUSIONS In this group of Mexican urban pregnant women, a serum glucose screening value of > or = 9.4 mmol (> or = 170 mg/dl) had a PPV of 85%. An algorithm is proposed to reduce the number of OGTTs performed in pregnant women attending prenatal care by 36.2%.

The prevalence of overweight and obesity is rising in pregnant as well as non‐pregnant Mexican women. A pre‐pregnancy BMI ≥ 25 increases the risk of adverse pregnancy outcomes. Simple anthropometric measurements may help identify pregnant women at risk of metabolic diseases, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). The aim of this study was to determine if anthropometric measurements are associated with the diagnosis of GDM among pregnant Mexican women. We collected anthropometric data (weight, height, skin folds, hip and waist perimeters) at 20, 24 and 28 wks in 34 women without any metabolic disease at booking. Nine of the 34 women were diagnosed with GDM at 28 wks. At all time points, body fat percentage (BFP), estimated by the Durnin equation with the sum of 4 skin folds, was significantly higher among women with GDM (Normal (n=25) 36.2% ± 0.8, 36.2% ± 0.7, 36.6% ± 0.7 vs GDM (n=9) 37.9% ± 1.3, 38.4% ± 1.3, 38.5% ± 1.2; p<0.001). Waist and hip perimeters at 20 wks correlated with BFP at 28 wks (r=0.547, p≤0.001; r=0.655, p≤0.001). The BFP at 28 wks was also associated with a GDM diagnosis (r=0.400, p=0.026). These data show that simple anthropometric measurements are useful tools for identifying Mexican pregnant women at risk for developing GDM. Partially support by UCMEXUS and Bristol Myers Squibb.

The aim of this study was to determine in pregnant women with systemic lupus erythematosus (SLE) the frequency of anti-prolactin autoantibodies and to compare the outcome of pregnancy in SLE women with and without anti-prolactin autoantibodies. Ninety-nine consecutive SLE pregnant women and 151 healthy pregnant women were studied prospectively. Patients with or without anti-prolactin autoantibodies were identified by gel filtration chromatography and affinity chromatography for IgG. Serum total and free prolactin (PRL) levels and molecular heterogeneity of PRL at each trimester of pregnancy were determined. The frequency of anti-PRL autoantibodies in SLE pregnant women was 13.1%. Serum total PRL levels were significantly higher in women with anti-PRL autoantibodies compared with SLE women without anti-PRL autoantibodies and in healthy pregnant women; and serum free PRL levels were lower in the third trimester in women with anti-PRL autoantibodies than in healthy pregnant women. In contrast, serum total and free PRL levels were significantly lower in the second and third trimester in SLE pregnant women without anti-PRL autoantibodies compared with healthy pregnant women. All adverse outcomes of pregnancy studied were more frequent in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women. Moreover, both maternal and fetal main complications were significantly higher in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women (P =0.03). We conclude that the frequency of anti-PRL autoantibodies in lupus pregnancy was 13.1%. SLE pregnant women with anti-PRL autoantibodies had fewer adverse outcomes of pregnancy. The presence of anti-PRL autoantibodies could be of potential use as a prognostic marker for outcomes of pregnancy in SLE.

Impaired glucose tolerance (IGT) is considered a pre-diabetic state. Its diagnosis early in pregnancy offers an opportunity to prevent development of gestational diabetes. A glucose challenge test (GCT) is routinely performed in Mexican pregnant women to assess glucose tolerance and the risk for IGT. The objective of this study was to identify factors associated with a high risk of developing IGT among Mexican pregnant women. We collected anthropometric, dietary, psychological, and socioeconomic data from 45 women at ≤ 20 weeks of pregnancy when a 50 g GCT was performed. At this point, fasting plasma glucose concentrations were measured. Mean age, gestational age, parity, and BMI were 29.8±10.7, 17±2.3, 3±1 and 26.3±5.1, respectively. The odds ratio of having an abnormal blood glucose 1 hour post-glucose challenge (≥130 mg/dL) were 10.7 higher among women with pre-pregnancy body mass index (PPBMI) >23 (p=0.02 CI 1.2–92.2) and 12 times higher with >5 previous pregnancies (p=0.01, CI=1.97–120.3). Fasting plasma glucose (FPG) concentrations >108 mg/dL also were significantly associated with an abnormal GCT (p=0.02). These preliminary data suggest that women with FPG >108 mg/dL, PPBMI≥23 and/or >5 pregnancies could be used for identifying Mexican women at risk of developing glucose intolerance during pregnancy. Partially support by UCMEXUS.

Vasoconstriction and defective placental angiogenesis are key factors in the etiology of preeclampsia. Prolactin levels are elevated in maternal blood throughout pregnancy and the human decidua produces prolactin that is transported to the amniotic fluid. Prolactin is cleaved to yield vasoinhibins, a family of peptides that inhibit angiogenesis and nitric oxide-dependent vasodilation. Here, we conducted a case–control study to measure vasoinhibins in serum, urine, and amniotic fluid obtained from women with severe preeclampsia. We show that all three biological fluids contained significantly higher levels of vasoinhibins in preeclamptic women than in normal pregnant women. Amniotic fluid from preeclamptic women, but not from normal women, inhibited vascular endothelial growth factor-induced endothelial cell proliferation and nitric oxide synthase activity in cultured endothelial cells, and these actions were reversed by antibodies able to neutralize the effects of vasoinhibins. Furthermore, amniotic fluid does not appear to contain neutral prolactin-cleaving proteases, suggesting that vasoinhibins in amniotic fluid are derived from prolactin cleaved within the placenta. Also, cathepsin- D in placental trophoblasts cleaved prolactin to vasoinhibins, and its activity was higher in placental trophoblasts from preeclamptic women than from normal women. Importantly, birth weight of infants in preeclampsia inversely correlated with the extent to which the corresponding AF inhibited endothelial cell proliferation and with its concentration of prolactin+vasoinhibins. These data demonstrate that vasoinhibins are increased in the circulation, urine, and amniotic fluid of preeclamptic women and suggest that these peptides contribute to the endothelial cell dysfunction and compromised birth weight that characterize this disease.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.

To investigate whether the long-term administration of metformin or pioglitazone to women with polycystic ovary syndrome (PCOS) could induce changes in their hypothalamic dopaminergic (DA) tone and to analyze whether these changes correlated with modifications in insulin resistance, we originally studied 57 obese hyperinsulinemic, non-diabetic, insulin resistant women with PCOS, but only 34 completed the study. They were randomly divided into two groups: group one (n=17) received pioglitazone (30 mg/day) and group 2 (n=17) received metformin (850 mg, three times a day) over 24 weeks. All women were identically studied before (basal) and 6 months after (T6) drug administration, including clinical evaluations, a 2 h oral glucose tolerance test (75 g) (OGTT) for glucose and insulin measurements, followed a week later by a 2 h intravenous metoclopramide test (10 mg bolus) for prolactin (PRL) determinations. The areas under the insulin (AUC-insulin) and PRL (AUC-PRL) curves were calculated, along with the index of insulin resistance (HOMA-IR) and the indexes of insulin sensitivity (QUICKI and fasting glucose-insulin ratio). At baseline, women in both groups were of similar age, body weight, body mass index (BMI) and Ferriman-Gallwey hirsutism score (F-G score). At completion of the study, body weight and BMI remained unchanged but the F-G score significantly decreased. Fasting serum insulin concentrations and the AUC-insulin significantly decreased by the end of the trial in a similar fashion in both groups, while the AUC-PRL significantly increased at the end of the trial in both groups. At no time were significant correlations between AUC-PRL and AUC-insulin or the indexes HOMA-IR, QUICKI or fasting glucose-insulin ratio observed. The present results suggests that either pioglitazone or metformin administration was associated with a clear improvement in the endogenous hypothalamic DA tone, simultaneously with an amelioration of the insulin resistance status in these obese women with PCOS.

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P </= 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P < 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P < 0.002) or metformin (P < 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P </= 0.008) after treatment with either drug. Hirsutism (P < 0.05) and serum concentrations of free testosterone (P < 0.02) and androstenedione (P < 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.

The precise etiologic mechanisms involved in the premature rupture of membranes (PROM) during pregnancy, the main cause of preterm delivery worldwide, are unknown. Previous studies have shown that:(a) the rupture of chorioamniotic membranes is related to an imbalance between synthesis and degradation of collagen induced by the overexpression/activity of various matrix metalloproteinases (MMP);(b) during human labor and delivery the expression of prolactin receptors (PRL-R) increases in chorioamniotic membranes, decidua and placenta;(c) prolactin (PRL) can influence the synthesis of prostaglandins, the expression of some MMP (MMP-2, MMP-9 and decysin) and tissue inhibitors of MMP in general;(d) vitamin C deficiency induces the expression/activity of extracellular MMP and is considered a risk factor for PROM; and(e) vitamin C potentiates the dopamine-mediated inhibition of PRL in rats.The present hypothesis proposes that a decreased hypothalamic dopaminergic tone-and thus an increased synthesis/release of pituitary PRL - is induced by vitamin C deficiency below a critical threshold (< 18 mug/10(8) leukocytes) and that both factors, in turn, would cause upregulation of the expression/activity of several MMP. The increased PRL concentrations (acting like a Th1-type cytokine) along with the overexpression of other proinflammatory cytokines would induce a premature switch from a favorable Th2-type immune response to a noxious Th1-type immune response in the intrauterine environment. This change, in conjunction with the upregulation of MMP-2 and MMP-9, would cause a premature imbalance between synthesis/degradation of collagen in chorioamniotic membranes (an "anticipation" of the normal parturition cascade?), which favors extracellular matrix degradation, proposed as the most relevant event in the genesis of PROM. This hypothesis represents a new dimension in the study of the etiology of PROM. (C) 2004 Elsevier Ltd. All rights reserved.

The existence of decreased hypothalamic dopaminergic tone in HIV-infected men has been suggested. In a cross-sectional study, we determined 12 h nocturnal basal and pulsatile prolactin (PRL) release levels (by blood sampling every 10 min) and their correlation with CD4+ T cells in seven volunteer HIV-negative, healthy men (group 1), and 21 normoprolactinemic, euthyroid, HIV-infected men divided into 3 groups (each group = 7): (i) group 2, asymptomatic HIV-infected stage A1 men, untreated; (ii) group 3, AIDS stage C3 without active opportunistic infections, untreated; and (iii) group 4, previously stage C3 after at least 6 months of successful highly active antiretroviral therapy. Serum PRL was measured by radioimmunoanalysis and the results were analysed by waveform-independent deconvolution analysis. CD4+ T lymphocytes were measured by flow cytometry and viral load by a nucleic acid sequence-based amplification assay. No differences were detected in the first two groups. In the third group, however, 100% of prolactin secretion was found to be pulsatile with a shorter secretory burst duration ( P = 0.04), and a greater circulating half-life and pulse amplitude ( P ≤ 0.04). Group 4 had the greatest basal prolactin secretion ( P ≤ 0.04), and a shorter secretory burst duration ( P = 0.04 vs group 2), circulating half-life ( P = 0.01 vs group 3) and intersecretory burst interval ( P = 0.06 vs group 1). PRL approximate entropy was similar among all groups. Linear correlations existed between CD4+ T cell counts and PRL secretory burst half duration ( r = 0.62, P = 0.002) and amplitude ( r = −0.63, P = 0.001), and in circulating serum half-life ( r = − 0.61, P = 0.002) in HIV-infected groups. Viral load showed no correlations. It is suggested that differential changes in nocturnal prolactin secretion among HIV-infected men occurred while maintaining the normal coordinate feedback and/or feedforward control within the lactotropic axis. These changes may represent an adaptative mechanism to sustain, by different means, the maximal physiologic PRL production to stimulate the highest cellular immune response and/or reconstitution in attempting to survive.