Healthy Non-pregnant Subjects Research Articles

Optical Coherence Tomography Angiography Evaluation of Retinochoroidal Microvascular Circulation Differences in Pregnant Women with Pregestational and Gestational Diabetes Mellitus.

In this study, the changes in microvascular circulation caused by pregestational and gestational diabetes were observed, without focusing on retinal findings, to reveal the effect of diabetes regulation. A total of 135 subjects were included: 30 with gestational diabetes (GDM), 30 pregestational diabetes (PGDM), 30 healthy pregnant normoglycemic subjects, and 45 healthy non-pregnant subjects. All subjects were examined by optical coherence tomography (OCT) and angiography. The retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), choroidal thickness (CT), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), vascular density (VD), and foveal avascular zone (FAZ) areas were measured. The foveal VD of SCP and DCP was significantly lower in the PGDM and GDM groups compared to the control groups (p:0.006 and p:0.001, respectively). CC VD was significantly higher in all pregnant groups compared to non-pregnant controls (p<0.001). The choroidal thickness values were highest in the healthy pregnant group and lowest in the PGDM group. There was no significant difference in FAZ area, retina, RNFL and GCL thickness between the groups. In the PGDM group, a negative correlation was observed between the FAZ area and the HbA1c level (r:- 0.417, p:0.043). There was a decrease in vascular density in pregnant women with diabetes compared to healthy pregnant women and controls. In the pregnant group with PGDM, a narrowing of the FAZ area was observed with increasing worsening of diabetes control. Diabetes type and glycemic control could influence the microvascular changes even in the absence of clinical or retinal findings.

The relationship between complete hydatidiform mole and serum Vitamin D level: a prospective case-control study.

This study aimed to determine whether or not there was a relationship between complete hydatidiform mole (CHM) and serum Vitamin D level by comparing CHM patients with two control groups and to determine whether or not Vitamin D deficiency is a risk factor for CHM. This prospective study included 30 patients diagnosed with CHM (case group), 30 patients in the first trimester of a healthy pregnancy (control group), and 30 healthy non-pregnant subjects (control group). A record was made of serum 25-hydroxyvitamin D (25-OH D vitamin) levels, age, body mass index (BMI), gravida, parity, and the number of abortus. The serum 25-OH D vitamin levels were examined in each group and compared between groups. The 25-OH D vitamin level of all the patients in the study was determined as 11.16±8.64 ng/mL. No significant difference was determined between the groups in respect of 25 OH-D vitamin levels. When comparisons were made between the four subgroups according to the 25-OH-D level, no significant difference was determined between the CHM and control groups. When the patients were separated as obese and non-obese groups, no significant difference was determined between the groups. Severe deficiency, deficiency, or insufficient levels of serum Vitamin D are not thought to be risk factors for CHM patients.

Analysis of retinal neurodegeneration in gestational and type 2 diabetes using swept-source optical coherence tomography

ObjectiveThis study aimed to compare the retina and choroid thickness in age-matched pregnant individuals with gestational diabetes mellitus, nonpregnant diabetic females, and healthy nonpregnant females. MethodThis cross-sectional study included 2 study groups, 1 composed of pregnant women with gestational diabetes mellitus and 1 consisting of nonpregnant type 2 diabetic patients without diabetic retinopathy, and a control group of healthy nonpregnant subjects. Swept-source optical coherence tomography was used to measure the retinal and choroidal thickness. The measurements were compared between the study groups and between the study groups and the control group. ResultsAll groups had similar mean ages, best-corrected visual acuity, and intraocular pressure (p = 0.122, p = 0.158, and p = 0.186, respectively). The mean central macular thickness of the gestational diabetes, type 2 diabetes, and control groups was 215.3 ± 10.83, 220.58 ± 21.62, and 230.03 ± 21.24 μm, respectively (p = 0.002). The retinal nerve fibre layer was slightly thinner only in the inferior zone of the study groups (p = 0.058) compared with the control group. We observed statistically significant differences in the thickness of all sectors of the ganglion cell layer between all groups (all p < 0.05), with the nonpregnant type 2 diabetic group exhibiting the lowest values. A similar mean subfoveal choroidal thickness was observed in all 3 groups (p = 0.247). ConclusionSwept-source optical coherence tomography plays an important role in detecting retinal neurodegenerative changes and choroidal thickness induced by gestational and type 2 diabetes before the development of diabetic retinopathy.

Methylglyoxal, Glycated Albumin, PAF, and TNF-α: Possible Inflammatory and Metabolic Biomarkers for Management of Gestational Diabetes.

Background: In gestational diabetes mellitus (GDM), pancreatic β-cell breakdown can result from a proinflammatory imbalance created by a sustained level of cytokines. In this study, we investigated the role of specific cytokines, such as B-cell activating factor (BAFF), tumor necrosis factor α (TNF-α), and platelet-activating factor (PAF), together with methylglyoxal (MGO) and glycated albumin (GA) in pregnant women affected by GDM. Methods: We enrolled 30 women whose inflammation and metabolic markers were measured at recruitment and after 12 weeks of strict dietetic therapy. We compared these data to the data obtained from 53 randomly selected healthy nonpregnant subjects without diabetes, hyperglycemia, or any condition that can affect glycemic metabolism. Results: In pregnant women affected by GDM, PAF levels increased from 26.3 (17.4–47.5) ng/mL to 40.1 (30.5–80.5) ng/mL (p < 0.001). Their TNF-α levels increased from 3.0 (2.8–3.5) pg/mL to 3.4 (3.1–5.8) pg/mL (p < 0.001). The levels of methylglyoxal were significantly higher in the women with GDM (p < 0.001), both at diagnosis and after 12 weeks (0.64 (0.46–0.90) μg/mL; 0.71 (0.47–0.93) μg/mL, respectively) compared to general population (0.25 (0.19–0.28) μg/mL). Levels of glycated albumin were significantly higher in women with GDM (p < 0.001) only after 12 weeks from diagnosis (1.51 (0.88–2.03) nmol/mL) compared to general population (0.95 (0.63–1.4) nmol/mL). Conclusion: These findings support the involvement of new inflammatory and metabolic biomarkers in the mechanisms related to GDM complications and prompt deeper exploration into the vicious cycle connecting inflammation, oxidative stress, and metabolic results.

Serum Immunoglobulin Changes in Pregnancy Complicated with Pre-Eclampsia and Diabetes in Nigerian Women

Objectives: Serum concentrations of IgA, IgG and IgM were determined in subjects with pre-eclampsia and gestational diabetes as compared to both apparently healthy pregnant and non-pregnant subjects resident in Port Harcourt, Nigerian. Materials and methods: A total of 200 femalesubjects comprising four groups of 50 subjects each were recruited into the study: healthy non-pregnant subjects (Group A); healthy pregnant subjects (Group B); subjects with pre-eclampsia (Group C) and subjects with gestational diabetesmellitus (Group D). All pregnant subjects were further subdivided into the appropriate semester according to gestational age of pregnancy. Venousblood samples were obtained and determined for immunoglobulins A, G and M with theturbidimetric immunoassay method usingan automated chemical analyzer. Results: Significant differences were observed in the values of the various types of immunoglobulins studied between healthy HIV sero-negative non-pregnant (group A) subjects and healthy HIV sero-negative pregnant (group B) subjects. Noteworthy is the observation that the values of both IgG and IgM were significantly higher while the values of IgA were significantly lower amongst the non-pregnant subjects in group A, compared to all the other pregnant subject groups: B, C and D (p<0.05). Furthermore, group B subjects were found to have significantly higher values of IgG and lower levels of IgM compared to groups C and D subjects (p<0.05). Values of IgA were significantly higher (P<0.05) in all pregnant groups compared to the non-pregnant subjects but highest in the GDM (group D) women.During the course of gestation, a graded decrease in the mean values of all three immunoglobulin classes was observed in the healthy pregnant group from the 1 st to 3 rd trimester. However, whereas a graded increase in mean IgA and IgM were observed in group C subjects across trimesters, mean IgG showed a similar graded but significant decrease (P<0.05). Also, the mean IgG decreased significantly in the pregnant diabetic (D) group in the 2 nd trimester,but that of IgM significantly increased in the 2 nd trimester. Conclusion: The observed changes in immunoglobulins A, G and M levels may be indicative of poorly transferred secondary immunity in the children born to pregnant diabetic and pre-eclamptic women, as well as pose complications related to indirect immune responses in these conditions.

Lipid-lysine adducts and modified tyrosines as markers of oxidative stress in the second trimester of pregnancy and their association with infant characteristics.

Pregnancy is a physiological state accompanied by excessive levels of oxidative stress (OS), due to the increased demand and utilisation of oxygen. There is increasing evidence that maternally augmented OS exerts an adverse effect on pregnancy outcome. The aim of the present prospective study was to determine the association between the urinary concentration of relatively novel OS markers measured in the second trimester of pregnancy and the infant characteristics at birth. The maternal levels of urinary hexanoyl-lysine (HEL), propanoyl-lysine (PRL), dityrosine (DiY) and 3-nitrotyrosine (NY) were evaluated in generally healthy pregnant subjects to determine their association with birth weight, gestation at delivery and Apgar score. The observed levels of the markers were in agreement with those measured in healthy non-pregnant subjects in a previous study. A positive correlation was detected between HEL and PRL, as well as between HEL and DiY. Although the absence of a correlation between NY and the other markers has been previously noted in a non-pregnant population, a positive correlation in the pair PRL-NY (r=0.367; P<0.001) was observed in the present study. Maternal cigarette smoking was associated with increased urinary PRL levels (P=0.034). The most notable observation in the present study was that high levels of PRL and NY were associated with low Apgar scores at 1 and 5 min after birth (OR, 1.098 and 2.084 for PRL and NY, respectively; P<0.05). However, poor predictive accuracy was shown. For NY, the following results were obtained: Area under the curve (AUC), 0.818; sensitivity, 100%; specificity, 57%; positive predictive value (PPV), 11.54%; and negative predictive value (NPV), 100%. For PLR the values were as follows: AUC, 0.802; sensitivity, 100%; specificity, 62.6%; PPV, 13.05%; and NPV, 100%. DiY was negatively associated with preterm birth risk (OR=0.703; P=0.028). In conclusion, the results of the present study indicated the presence of OS in the second trimester of pregnancy, which was detected with damage to lipids and proteins and associated with an adverse Apgar score; however, the selected urinary markers exhibited poor positive predictive efficacy.

A study on cardiac autonomic modulation during pregnancy by non-invasive heart rate variability measurement

Purpose: Remarkable and uncontrollable changes with modification during pregnancy are connected with the autonomic control and consequently with the heart rate variability (HRV). Heart rate variability is a sum of different mechanisms and if pregnancy is a state of change, these modifications could be extracted from HRV analysis. Objective: To assess the effect of pregnancy on heart rate variability among pregnant mothers during first trimester of pregnancy and third trimester of pregnancy. Materials and Methods: HRV was measured for 5 minutes of continuous recording of electrocardiogram (ECG) lead II, using windows based HRV analysis system variowin-HR after obtaining permission from the Institutional Review Board of Government Medical College, Bhavnagar and written consent from 30 pregnant subjects and 30 non-pregnant control subjects at autonomic function lab, Dept of Physiology, Bhavnagar. Result: Frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF) and HF normalized unit (nu) were significantly decreased and LF (nu) and LF/HF significantly increased in pregnant subject in 3 rd trimester as compared to their 1 st trimester of pregnancy. Time Domain parameters like SDNN, RMSSD, SDSD, NN50 count, pNN50, SD1/SD2, triangular HRV index and average R-R interval were significantly decreased during 3 rd trimester of pregnancy. Conclusion: The inhibition of resting parasympathetic activity or vagal blockage and an increment of the sympathetic modulation during the 3 rd third trimester of gestation in pregnancy as compared to their 1 st trimester and healthy non-pregnant subjects. Sympathovagal imbalance and abnormally low HRV may more pronounce during later stage of normal pregnancy.

Reference ranges of serum TSH, FT4 and thyroid autoantibodies in the Thai population: the national health examination survey

Data on reference intervals of thyroid functions in Southeast Asia are limited. The aim of this study was to provide reference ranges of thyroid functions and thyroid autoantibodies in Thais. Serum samples from 2545 apparently healthy non-pregnant subjects, aged ≥14 years, from the fourth Thai National Health Examination Survey were measured for TSH, FT4, antithyroperoxidase (TPO Ab), antithyroglobulin (Tg Ab) and antithyrotrophin receptor antibodies (TRAb). A reference population was selected from the disease-free population by excluding those who had thyroid autoantibodies and TSH > 20 mIU/l. For the total population, median TSH and FT4 levels were 1·94 mIU/l and 1·35 ng/dl, respectively. TSH was higher and FT4 was lower in females than in males. Based on National Academy of Clinical Biochemistry criteria, the reference intervals (2·5th-97·5th percentile) were: TSH, 0·34-5·11 mIU/l; FT4, 0·98-1·79 ng/dl; TPO Ab, 5-84·88 IU/ml; Tg Ab, 10-118·2 IU/ml; and TRAb, 0·3-1·24 IU/l. With the new reference ranges, hypothyroidism was found in 4·16% of the total population (0·78% overt and 3·38% subclinical hypothyroidism) and hyperthyroidism was found in 3·18% (0·94% overt and 2·24% subclinical hyperthyroidism). Positive TPO Ab, Tg Ab and TRAb were found in 8·96%, 12·26% and 5·93%, respectively. The upper normal limit of TSH tended to increase with age, particularly for those aged 80 years and older. The reference interval for TSH needs to be derived from each specific population. Slightly elevated TSH concentrations in the elderly could be considered acceptable, with no need for thyroxine treatment.

Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy

Wickström K, Edelstam G, Löwbeer Ch, Hansson L-O, Siegbahn A. Reference intervals for plasma levels of flbronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest 2004; 64: 31-40.During pregnancy, significant changes occur in the hemostatic system and in the plasma levels for several plasma proteins, especially towards term. In this study changes occurring during normal pregnancy and immediately postpartum were investigated to establish adequate reference intervals for important hemostatic parameters. Blood samples were collected during pregnancy weeks 33, 36, 39 and 1-3 h after delivery from 153 healthy pregnant women with at least one previous normal pregnancy. The plasma samples were analyzed for antithrombin, von Willebrand factor (vWf), free protein S and flbronectin. Fibroncctin and vWf are contact-promoting proteins responsible for adhesion and aggregation during primary hemostasis, but are also released from thrombocytes during activation of the coagulation process. Antithrombin is the most important primary physiological inhibitor of activated serine proteases related to the coagulation cascade. Protein S is a co-factor to protein C and in cooperation is also an important inhibitor of the coagulation cascade. During third-trimester pregnancy, vWf was higher than in non-pregnant women, and continued to increase postpartum. The flbronectin plasma level was mostly unchanged in comparison with non-pregnant values. Within this reference interval it gradually increased during the third trimester, but fell slightly postpartum. Antithrombin decreased slightly during the third trimester and even further, postpartum. Free protein S decreased markedly but to a stable level from week 33 to 39, decreasing even more postpartum. The present results are concordant with clinical knowledge of increased risk of thrombosis during pregnancy and early Puerperium, with increased levels of vWf and fibronectin and decreased levels of antithrombin and free protein S. Clearly, current reference values based on healthy non-pregnant subjects are not usable during late pregnancy and immediately postpartum.

Decrease in Plasminogen Activator Inhibitor Type 2 Related More to Placental Function and Intrauterine Fetal Growth than to Severity of Preeclampsia

Objectives: To evaluate changes in levels of plasminogen activator inhibitor type 2 (PAI-2) during preeclamptic pregnancies. To assess whether the changes are related to placental and/or fetal complications, and to the severity of preeclampsia.Methods: Concentrations of plasma PAI-2 were measured in 21 normal pregnant women, 94 preeclamptic patients, and 2 patients with hydatidiform mole. Comparisons were made between the respective groups.Results: Significantly higher PAI-2 levels were shown in the pregnant women with or without preeclampsia than in healthy nonpregnant subjects (P 0.05). In the patients with molar disease, no PAI-2 antigen was detected....

Reaction of peripheral-blood lymphocytes to the human chorionic gonadotropin beta sub-unit in patients with productive tumors.

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCG beta sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCG beta can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 31% of patients with hCG beta-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCG beta-specific proliferative response, whereas no patients with non-hCG beta-productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCG beta were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DQ2 haplotype, the T-cell response to hCG beta was focused on the hCG beta (20-47) peptide. Taken together, these results indicate that hCG beta is a tumor-associated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.

Test Doses

The authors studied the optimal epinephrine content of an epidural test dose, and determined criteria to identify intravascular injections in subjects with or without beta-adrenergic blockade. Nine healthy nonpregnant subjects 25-36 years of age were given intravenous infusions of saline or esmolol in random order. During each infusion, they received a series of five injections (3 ml each) of either saline, 1% lidocaine or 1% lidocaine containing 5, 10, or 15 micrograms of epinephrine. Thirty minutes after completing these two infusions, propranolol was administered as a bolus injection, and the series of five injections repeated. All injections were double blind and randomized. During saline infusion, all injections containing epinephrine significantly increased heart rate (HR) by an average of 31-38 beats/min when compared with that following plain lidocaine (P less than 0.05), and increased systolic blood pressure by an average of 17-26 mmHg (P less than 0.05 for the 15-micrograms dose only). During esmolol infusion, epinephrine injections increased HR by an average of 23-31 beats/min (P less than 0.05), and increased systolic blood pressure by an average of 18-30 mmHg (P less than 0.05 for 10 and 15 micrograms). After propranolol injection, epinephrine injections caused a decrease in HR by an average of 21-28 beats/min (P less than 0.05), whereas systolic blood pressure increased by an average of 22-35 mmHg (P less than 0.05 for 10 and 15 micrograms only). Without beta-adrenergic blockade, an increase in HR greater than or equal to 20 beats/min was 100% sensitive and specific for intravascular injection of 10 or 15 micrograms of epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Disparity betweenβ-Core Levels in Pregnancy Urine and Serum: Implications for the Origin of Urinaryβ-Core

We used a highly purified preparation of the naturally occurring core fragment of hCG beta (beta-core) and a new RIA for beta-core to investigate the concentrations and behavior of beta-core in serum and urine. We collected serum and 24-h urine specimens from healthy pregnant women during the first trimester of pregnancy. The concentrations of beta-core in serum were determined by analysis of fractions eluted from Sephadex G-100. Serum concentrations of beta-core immunoreactivity were very low (0.13-1.25 micrograms/L), while large amounts of beta-core were excreted in urine during pregnancy (as much as 4-5 mg/day). Interference with measurement by serum factors did not account for the low levels of beta-core immunoreactivity in pregnancy serum. Based on the known urinary clearance rate of beta-core in healthy nonpregnant subjects, we calculated that urinary clearance of serum beta-core accounts for only about 1% of the beta-core in pregnancy urine. We conclude that during pregnancy, the concentrations of beta-core in plasma are measurable, but extremely low, and that most of the beta-core in urine is derived by mechanisms other than urinary clearance of serum beta-core; most likely, these mechanisms involve nephrogenous production of beta-core from precursor molecules such as hCG and hCG beta.

Folic acid safety and toxicity: a brief review

Oral folic acid (pteroylglutamic acid) is generally regarded as not toxic for normal humans but it may cause neurological injury when given to patients with undiagnosed pernicious anemia. The vitamin should be given with caution to drug-treated epileptic patients because seizure control may be affected. Some studies suggest that folic acid supplements interfere with intestinal zinc absorption in humans and animals but others do not confirm such an effect. The weight of current evidence favors the view that daily supplements of 5-15 mg folic acid do not have significant adverse effects on Zn nutriture in healthy nonpregnant subjects. Because antifolate medications are now being used to treat a wide range of malignant and nonmalignant disorders, further investigation is needed concerning folate metabolism and the safety of supplements in patients with these disorders.

Clinical usefulness and false-positive results of CA 125 as a tumor marker of ovarian cancer--a study on 674 patients.

To study the clinical usefulness and false-positive results of CA 125 as a tumor marker of ovarian cancer, we measured serum CA 125 levels in 197 patients with gynecological diseases, 274 normal, pregnant and postpartum women, 14 patients with abnormal pregnancy, 82 healthy women with a normal ovulatory menstrual cycle and 107 healthy non-pregnant subjects, using RIA kits. A level below 34 U/ml was considered the normal CA 125 range. The positive ratio of serum CA 125 in patients with malignant ovarian tumor was 81.3 per cent, and in those with serous cystadenocarcinoma the rate was 100 per cent. On the other hand, only one patient with benign ovarian tumor had a positive CA 125 value. Therefore, we suggest that CA 125 is useful for differentiation between benign ovarian tumor and ovarian cancer. However, because the positive ratio of CA 125 level is high in patients with recurrences of uterine cervical adenocarcinoma, those with tubal cancer, endometriosis, early pregnancy, abnormal pregnancy plus intrauterine fetal death and menstruating women, such situations must be given due attention when CA 125 is used as a tumor marker of ovarian cancer.

Levels of placenta-specific tissue protein 12 (PP12) in serum during normal pregnancy and in patients with trophoblastic tumour.

A sensitive radioimmunoassay method has been developed to measure soluble placental protein 12. Using this method trace amounts of PP12 have also been detected in the sera of healthy non-pregnant subjects (24.0 +/- 6.15 micrograms/l). During normal pregnancy serum PP12 levels rose rapidly reaching a peak value of 139.90 +/- 40.26 micrograms/l at 18 weeks. Serial determinations of PP12 have been made in 31 patients with trophoblastic tumours (16 hydatidiform moles, 10 invasive moles and five choriocarcinomas). It has been found that in patients with hydatidiform and invasive moles its initial values are extremely high (342.9 +/- 257.9 micrograms/l and 279.3 +/- 103.1 micrograms/l, respectively), much exceeding the non-pregnant and normal pregnant values. After evacuation of hydatidiform moles serum-PP12 rapidly fell to the upper limit of normal at 21-28 days, and to normal values at 8-12 weeks after operation. In patients with invasive mole requiring chemotherapy the rate of fall of PP12 level was slower. In patients with choriocarcinoma serum-PP12 levels were moderately raised (59-132 micrograms/l) and followed the clinical course of the disease. Serum-PP12 levels would seem to be of less value in monitoring patients with trophoblastic tumours than other tumour-markers (hCG, and SP1).

Serum fibrin degradation products throughout normal pregnancy.

Fibrin/fibrinogen degradation products in the serum of 169 healthy pregnant and 43 healthy non-pregnant subjects of a similar age group showed a significant increase throughout pregnancy, the highest levels being obtained in the third trimester. There was no correlation with plasma fibrinogen levels or euglobulin lysis times. Though these changes may be due to other alterations in pregnancy not primarily associated with fibrinolysis, it is possible that actual fibrinolysis is not decreased in late pregnancy, as has been previously asssumed.