Identification of potential serum metabolic biomarkers for patient with keratoconus using untargeted metabolomics approach.

This study aimed to investigate the metabolite differences between patients with keratoconus and control subjects and identify potential serum biomarkers for keratoconus using a non-targeted metabolomics approach. Venous blood samples were obtained from patients with keratoconus (n = 20) as well as from age-, gender- and race-matched control subjects (n = 20). Metabolites extracted from serum were separated and analyzed by liquid chromatography/quadrupole time-of-flight mass spectrometer. Processing of raw data and analysis of the data files was performed using Agilent Mass Hunter Qualitative software. The identified metabolites were subjected to a principal component and hierarchical cluster analysis. Appropriate statistical tests were used to analyze the metabolomic profiling data. Together, the analysis revealed that the dehydroepiandrosterone sulfate from the steroidal hormone synthesis pathway was significantly upregulated in patients with keratoconus (p < 0.05). Also, a combination of eicosanoids from the arachidonic acid pathway, mainly prostaglandin F2α, prostaglandin A2, 16,16-dimethyl prostaglandin E2, and 5-hydroxyeicosatetraenoic acid were collectively up-regulated as a group in keratoconus patients (p < 0.05). On the other hand, glycerophospholipid PS(17:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) was found to be significantly upregulated in the metabolomics profiles of control subjects (p < 0.05). The differently regulated metabolites provide insights into the pathophysiology of keratoconus and could potentially be used as biomarkers for keratoconus to aid in screening for individuals at risk hence, enabling early diagnosis and timely monitoring of disease.

High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. METHODS: We measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. RESULTS: Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P < 0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P < 0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P < 0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P < 0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r = 0.477-0.589, P < 0.05). CONCLUSION: The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Effects of a carrot juice intervention on plasma carotenoids, oxidative stress, and inflammation in overweight breast cancer survivors.

Evidence suggests that higher plasma carotenoid concentrations are protective in relation to breast cancer recurrence. This simple randomized carrot juice intervention study was designed to test the hypothesis that daily intake of 8 ounces of fresh BetaSweet (anthocyanin-rich) or Balero orange carrot juice would increase plasma total carotenoid concentrations to levels previously shown to be associated with reduced breast cancer recurrence. It was hypothesized that regular carrot juice intake would be associated with reductions in oxidative stress (8-iso-PGF2α) and inflammation (thromboxane B2, prostaglandin E2 metabolites, and hsC-reactive protein). Sixty-nine overweight breast cancer survivors consumed fresh carrot juice made from study-provided carrots for 3 wk. Total plasma carotenoids increased by 1.65 and 1.38 umol/L for the BetaSweet and Balero carrot juice, respectively. Rise in total plasma carotenoids for the overall sample was inversely associated with 8-iso-PGFα (OR: 0.13; 95% CI: 0.20 to 0.75; no differences were shown by carrot variety. These results suggest daily intake of fresh carrot juice is a simple and effective approach to increasing plasma total carotenoids and in turn reducing oxidative stress, but not inflammatory markers, in women previously treated for breast cancer.

[State of prostanoid-regulating function of the lungs in patients subjected to thoracic surgery]. / Sostoianie prostanoidreguliruiushchei funktsii legkikh u bol'nykh pri torakal'nykh operatsiiakh.

Lung capacity to regulate the level of plasma prostanoids at the expense of their destruction or extra synthesis is one of their numerous non-gas-exchange functions. Prostaglandins A, E, and F, prostacyclin, and thromboxane were measured in the arterial and venous blood of 23 patients before and after surgery. The level of prostanoids was sharply increased in surgical patients. Substrates with the broncho- and vasoconstrictive action predominate in the blood of patients with obstructive and restrictive changes in the lungs, this eventually leading to complications in the postoperative period.

High IgE serum levels and "peptic" ulcers: clinical and functional approach.

The prevalence of high total IgE serum levels was evaluated in 232 consecutive patients suffering from peptic ulcer. Twenty-one percent of the patients presented total IgE serum levels above 200 KU/L compared with the 5% found in a healthy control population (p < 0.004). Similar prevalence was found in gastric and/or duodenal ulcers. No significant differences in the duration of the disease, smoking habits, familiarity for peptic ulcer, symptomatology and frequency of complications were observed between patients with high and with normal total IgE serum levels. Gastric function studies (gastric acid secretion, serum pepsinogen and gastrin levels) did not show any significant differences between the two groups. The incidence of Helicobacter pylori infection was 65% in patients with normal IgE levels and 75% in those with high IgE levels (p: n.s.). The response to treatment with full dose of H2-receptor antagonists was comparable in both groups (91.25% and 90.7% of ulcer healing after 6-8 weeks of treatment). A relapse of the ulcer after 6 months of maintenance therapy (half dose of H2-receptor antagonists) was observed in 39.5% of the patients with ulcer and high total IgE serum as against the 11.9% observed in patients with normal IgE (p < 0.001). These data lend further support to the hypothesis of an underlying immuno-allergic reaction in some forms of gastric or duodenal ulcer.

[The role of prostaglandins in the development of associated late pregnancy toxicosis in hypertension patients]. / Rol' prostaglandinov v razvitii sochetannogo pozdnego toksikoza beremennykh u bol'nykh gipertonicheskoi bolezn'iu.

The plasma levels of prostaglandins A, E, and F2 alpha were measured by the radioimmunoassay in 146 hypertensive and 62 healthy pregnant females. It was ascertained that beginning in the second trimester, the ratio of various prostaglandins is impaired in the direction of increasing values of substances from the pressor group as the hypertensive disease evolves. This is due to lower levels of prostaglandins A and E and/or higher levels of prostaglandins F2 alpha. In associated late gestosis, prostaglandin levels are related to the clinical manifestations of this disease. There are increased prostaglandin F2 alpha concentrations with severe nephropathy. The studies indicate that prostaglandins affect the course of hypertensive disease in pregnant women and the development of associated late gestosis.

[The content of prostaglandins A and E in the blood and renal tissues in the early phase of experimental acute renal failure caused by the crush syndrome]. / Soderzhanie prostaglandinov grupp A i E v krovi i tkaniakh pochek v rannei faze éksperimental'noi ostroi pochechnoi nedostatochnosti, vyzvannoi krash-sindromom.

Prostaglandin (PG) A and E content in the blood and renal tissues (cortex and medulla) has been studied in 25 dogs in the early phase of acute renal failure (ARF). It has been found that by the 4th hour of compression PG content increases drastically in the blood and renal cortex and decreases in the renal medulla. Compression relief and ARF progress were accompanied by a drop in PG concentration both in the blood and the renal cortex and medulla. It is concluded that enhanced PGE2 synthesis is a protective reaction preventing the damage of the renal structure and function. The following decrease in PGE2 level is mediated by progressing effect of aggressive factors on the interstitial cells of the renal medulla and the endothelial cells of the cortex vessels--as a basic source of endogenous PG synthesis. The results obtained are experimental proof of PGE2 use in the complex therapy of ARF.

Clomifén como inductor de crecimiento folicular múltiple / Clomiphene as inductor of multiple follicular growth

En nuestro programa de FIV ñ TE y GOFT se administraron 100 mg de clomifén de los días dos al seis del ciclo, en 35 ciclos de 32 pacientes estériles. Se establecieron curvas de estadiol sérico asistidas por computadora, encontrándose tres tipos de curvas: 1. Curva ascendente, subdividida en curva A (seis ciclos) com estradidol mayor de 600 pg/mL, más de cuatro folículos con tamaño folicular promedio de 35 mm. Curva B (13 ciclos) con estradiol entre 300 y 600 pg/mL, 2.9 folículos de 24 mm en promedio y curva C con menos de 300 pg/mL de estradiol, 0.8 folículos de 22 mm en promedio. 2. Curva plana con un nivel estrogénico y tamaño folicular mínimos y 3. Curva irregular con variaciones atípicas que probablemente reflejen atresia de oocitos y formación de quistes. El nivel de progesterona en fase lútea paralelo al nivel de estradiol. Existió evidencia de crecimiento folicular múltiple en 40 ciclos (57%). Se realizaron nueve laparoscopias para captura ovular, obteniéndose 1.2 oocitos en promdedio por laparoscopia, se fertilizaron in vito y fueron transferidos cuatro embriones y se transfirieron a trompa cuatro oocitos. Sólo se obtuvo un oocito maduro por laparoscopia. No se lograron embarzos. El clomifén como agente único inductor de ovulación múltiple, por su disponibilidad, puede ser una alternativa por algunas mujeres que muestren buena respuesta, la que depende de varios factores, pero no puede considerse el agente ideal para los programas que incluyan captura ovular

Humoral factors involved in the regulation of sodium-fluid balance in man. III. Renal prostaglandins and renin-angiotensin-aldosterone system in hypertensive disorders.

An estimation of renal secretion rates of PGE2 and PGF2 alpha, in parallel with renin-angiotensin-aldosterone system and catecholamines was performed on control subjects, essential hypertensive, and renovascular hypertensive patients. In essential hypertensive patients with normal plasma renin activity (PRA) and normal catecholamines level. We did not find any changes in the renal prostaglandin (PG) secretion rate as compared to the control subjects. Our results do not support the hypothesis that a reduction of PGE2 production is a specific feature of patients with essential hypertension. In renovascular hypertensive patients with unilateral renal artery stenosis we found: 1. High PRA in the renal plasma of the abnormal (with renal artery stenosis) kidney, and in peripheral plasma; 2. Decreased renal release of PGE2 from both kidneys, more distinct in abnormal kidney; 3. No changes of renal production of PGF2 alpha. The positive and negative correlation between renin-angiotensin system and renal PGs in physiological and pathological conditions was discussed.

Thromboxane B2, 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 plasma levels in arteriosclerosis obliterans: relationship to clinical manifestations, risk factors, and arterial pathoanatomy.

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.97 +/- 320.86 pg/ml, mean +/- SD, vs 20 +/- 2.1 and 352.66 +/- 235.54 vs 24.4 +/- 3, p less than 0.01) were detected in arteriosclerosis obliterans patients. The ratio between TXB2 and 6-keto-PGF1 alpha was increased from 1.2 in control subjects to 6.0 in patients. In arteriosclerosis obliterans TXB2 increased in relation to clinical manifestations and to the extension of the vascular damage. In addition, TXB2 was positively related to serum triglyceride content (r = 0.562, p less than 0.05) and inversely related to platelet count (r = 0.727, p less than 0.001). The marked imbalance between the stable metabolites of thromboxane and prostacyclin in arteriosclerosis obliterans patients provides biologic evidence which fits well with the thrombogenic theory of atherosclerosis. These results further support the theory that prostaglandins may be heavily involved in atherosclerosis.

[Effect of chorionic gonadotropin on the content of prostaglandins (E + A) in pathologically altered liver tissue and blood of rats]. / Vliianie khorionicheskogo gonadotropina na soderzhanie prostaglandinov (E + A) v tkani patologicheski izmenennoi pecheni i v plazme krovi krys.

Twenty-four and 48 hours after injection of chorionic gonadotropin (CG) the content of prostaglandins E + A in the liver and blood plasma of white random-bred rats with chronic hepatitis increases (both after and without castration). This accounts for some aspects of the mechanism of the CG-induced stimulation of liver regeneration, which results in structural and functional normalization of the organ.

[Prostaglandins A1, E1 and F2 alpha concentrations in the arterial and coronary venous blood of patients with ischemic heart disease during induced myocardial ischemia]. / Soderzhanie prostaglandinov A1, E1, F2 alpha v arterial'noi i koronarnoi venoznoi krovi u bol'nykh ishemicheskoi bolezn'iu serdtsa pri indutsirovannoi ishemii miokarda.

Prostaglandins (PGA1, PGE1 and PGF2 alpha) were assayed in 15 patients with chronic coronary disease during an anginal attack induced through frequent atrial stimulation. Measurements from eleven patients with intact coronary arteries served as control. Lactate extraction coefficient was used as a biochemical indicator of myocardial ischemia; the latter was associated with increased production of coronary sinus PGF2 alpha and arterial PGA1. No correlation could be established between PG levels in the studied series, the extent of ST depression on electrocardiograms, lactate extraction level and hemodynamic manifestations.