Sensitivity to a neurosteroid is increased during addition of progestagen to postmenopausal hormone replacement therapy.

The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT). Twenty-seven postmenopausal women with climacteric symptoms were administered HRT in a randomized, double-blinded, placebo-controlled crossover study. The women received 2 mg estradiol (E2) continuously during four 28-day cycles and 10 mg medroxyprogesterone acetate (MPA), 1 mg norethisterone acetate (NETA) or placebo sequentially for the last 14 days in each cycle. The pharmacodynamic response to pregnanolone was assessed before treatment and during the last week of each treatment, by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV), saccade deceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. During the progesta gen phase of the treatment cycles, negative mood symptoms and physical symptoms were increased, whereas positive mood symptoms were decreased. Compared to pretretreatment conditions, E2 alone did not change the responsiveness to pregnanolone. During progestagen addition to E2, the responsiveness to pregnanolone was increased. The sedation response increased compared to pretreatment conditions during both E2 + MPA and E2 + NETA treatment. Compared to E2 treatment alone, addition of MPA increased the postpregnanolone effect on saccade deceleration, whereas the SEV response to pregnanolone was increased during E2 + NETA treatment. It is concluded that pregnanolone sensitivity increases together with deterioration in mood symptoms during addition of progestagen to HRT.     

Neuroactive pregnanolone isomers during pregnancy

The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels. The ratios of individual PI were similar to those found previously around parturition: about 25:10:7:1 for allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI showed a significant increase during pregnancy, which was more pronounced in the 3alpha-steroids. The results indicated changing ratios between 3alpha- and 3beta-PI and between 5alpha- and 5beta-PI throughout pregnancy. The constant allopregnanolone/isopregnanolone ratio found through pregnancy weakened the hypothesis of the role of isopregnanolone in the onset of parturition. The ratio of estradiol (stimulating uterine activity) to 5alpha-PI and epipregnanolone exhibited significant changes during pregnancy in favor of estradiol up to the sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio. A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating effect of estradiol on the onset of parturition, was suggested.     

The intestinal microflora and its colon cancer connection

Summary Epidemiologic studies suggest that the incidence of colon cancer is influenced by environmental factors, especially diet. The high beef-high fat-low fiber diet of Western societies is associated with a high risk of colon cancer. The intestinal microflora may play a role in colon cancer by metabolic activation of procarcinogens in the lumen of the large bowel. The link between diet and colon cancer can be explained, in part, by the alterations in fecal bacterial enzyme activity induced by a Western-style diet. For example, fecal bacterial -glucuronidase, nitroreductase, azoreductase and steroid 7--dehydroxylase activities are increased in animals or humans consuming a high beef diet. These enzyme activities can be reduced by eating a grain diet, by the addition ofLactobacillus acidophilus to the diet, or by administration of low dose antibiotics. In experimental animals these three measures to reduce the activity of the microflora also produce few colon tumors in animals given the chemical carcinogen dimethylhydrazine. Further studies are needed to establish whether alterations in the metabolism of the colonic microflora can reduce the risk of large bowel cancer in humans.

---

Die Darmflora und ihre Beziehung zum Kolonkarzinom

Zusammenfassung Epidemiologische Studien lassen annehmen, daß die Inzidenz des Dickdarmkarzinoms von Umweltfaktoren, insbesondere der Ernährung, beeinflußt wird. Die faserarme Nahrung westlicher Länder mit ihrem hohen Gehalt an Rindfleisch und Fett ist mit einem hohen Risiko für Dickdarmkrebs assoziiert. Die Mikroflora des Darmes beeinflußt möglicherweise den Dickdarmkrebs durch metabolische Aktivierung von Prokarzinogenen. Der Zusammenhang zwischen Ernährung und Kolonkarzinom kann zum Teil dadurch erklärt werden, daß westliche Ernährungsgewohnheiten die Enzymaktivität der Darmbakterien ändern. Bei Tieren oder bei Menschen, die mit viel Rindfleisch ernährt werden, sind beispielsweise die Aktivitäten der Darmbakterien-Enzyme -Glukuronidase, Nitroreduktase, Azoreduktase und Steroid-7--dehydroxylase erhöht. Durch Körnerdiät, durch Zusatz vonLactobacillus acidophilus zur Nahrung oder durch Gabe von nieder dosierten Antibiotika können diese Enzymaktivitäten vermindert werden. Diese drei Maßnahmen zur Verminderung der Aktivität der Mikroflora führen bei Laboratoriumstieren dazu, daß nach Gabe des chemischen Karzinogens Dimethylhydrazin nur wenige Kolontumoren auftreten. Daß Änderungen im Stoffwechsel der Darmflora auch beim Menschen das Risiko für den Dickdarmkrebs vermindern, muß erst durch weitere Untersuchungen belegt werden.

     

Effects of feeding cholesterol and mixed plant sterols on the fecal excretion of acidic steroids in rhesus monkeys

The effects of feeding diets with high or low amounts of cholesterol and with low or high levels of mixed plant sterols (sitosterol: campesterol: stigmasterol, 60:35:5) on the daily fecal excretion of acidic steroids were studied in rhesus monkeys. During periods of low dietary plant sterol, total fecal acidic steroid excretion was 43% lower (P less than 0.01) during low dietary cholesterol than during high dietary cholesterol. During periods of high dietary plant sterols the fecal acidic steroid excretion was 113% higher (P less than 0.01) with low dietary cholesterol than with high dietary cholesterol. Addition of mixed plant sterols to the low-cholesterol diet produced nearly a 2-fold increase (P less than 0.005) whereas, such an addition to the high cholesterol diet produced a significant decrease by about 53% (P less than 0.025) in the total fecal acidic steroid excretion. The results suggest that the effect of cholesterol feeding on fecal acidic steroid excretion depends on the level of plant sterols in the diet. This interaction of the effects of cholesterol and plant sterols on the fecal acidic steroid excretion is probably related to the inhibitory effect of plant sterols on cholesterol absorption.     

Reinstatement of serum pregnanolone isomers and progesterone during alcohol detoxification therapy in premenopausal women

BACKGROUND: Alcohol abuse is associated with menstrual irregularities related to the inhibition of progesterone secretion involved in regulation of the menstrual cycle. Reduced progesterone metabolites, including pregnanolone isomers (PIs), are efficient neuromodulators. The authors attempted to evaluate whether levels of PIs reflect impairment in progesterone biosynthesis in premenopausal women treated for alcohol addiction and whether alcohol detoxification therapy contributes to the restoration of their reproductive functions and psychosomatic stability by influencing steroid biosynthesis. METHODS: Serum allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; P3alpha5alpha), pregnanolone (P3alpha5beta), isopregnanolone (P3beta5alpha), epipregnanolone (P3beta5beta), progesterone, pregnanolone sulfate (PregS), pregnanolone, and estradiol were measured in 20 women during therapy (at start, three days, 14 days, one month, and four months) by gas chromatography-mass spectrometry or radioimmunoassay. The results were evaluated by a linear mixed model for longitudinal data, with stage of the treatment and subject as categorical factors, phase of the menstrual cycle as a time-varying covariate, and age of the subject as a covariate and by regression in individual stages of the menstrual cycle. RESULTS: During detoxification treatment, progesterone increased in the luteal phase. P3alpha5alpha, P3beta5alpha, and P3beta5beta rose in both phases of the menstrual cycle. DISCUSSION: Given the similar mechanism in the effects of alcohol and steroids in activating gamma-aminobutyric acid A receptors, the restoration of progesterone and PIs during therapy could be explained by an adaptation to increasing requests for gamma-aminobutyric acid A-receptor activating substances owing to the cessation of alcohol intake or by the regeneration of progesterone formation. In conclusion, the reinstatement of progesterone, P3alpha5alpha, and P3beta5beta serum levels demonstrates the favorable effect of detoxification therapy on both reproductive functions and the psychosomatic stability of premenopausal women treated for alcohol addiction.     

Clinical Significance of Fecal Lactoferrin and Multiplex Polymerase Chain Reaction in Patients with Acute Diarrhea

Background/AimsThe diagnostic yield of fecal leukocyte and stool cultures is unsatisfactory in patients with acute diarrhea. This study was performed to evaluate the clinical significance of the fecal lactoferrin test and fecal multiplex polymerase chain reaction (PCR) in patients with acute diarrhea.MethodsClinical parameters and laboratory findings, including fecal leukocytes, fecal lactoferrin, stool cultures and stool multiplex PCR for bacteria and viruses, were evaluated prospectively for patients who were hospitalized due to acute diarrhea.ResultsA total of 54 patients were included (male, 23; median age, 42.5 years). Fecal leukocytes and fecal lactoferrin were positive in 33 (61.1%) and 14 (25.4%) patients, respectively. Among the 31 patients who were available for fecal pathogen evaluation, fecal multiplex PCR detected bacterial pathogens in 21 patients, whereas conventional stool cultures were positive in only one patient (67.7% vs 3.2%, p=0.000). Positive fecal lactoferrin was associated with presence of moderate to severe dehydration and detection of bacterial pathogens by multiplex PCR (21.4% vs 2.5%, p=0.049; 100% vs 56.5%, p=0.032, respectively).ConclusionsFecal lactoferrin is a useful marker for more severe dehydration and bacterial etiology in patients with acute diarrhea. Fecal multiplex PCR can detect more causative organisms than conventional stool cultures in patients with acute diarrhea.     

Concentrations of four fecal steroids in wild baboons: short-term storage conditions and consequences for data interpretation

One source of both bias and "noise" in fecal steroid analysis is temporal change in steroid concentrations resulting from duration or conditions of fecal sample storage. However, no consensus currently exists regarding correct procedures or precautions necessary for fecal sample storage, and conditions vary widely within field endocrinology literature. This study considered the effects of short-term, weeks-long, storage conditions on quantifiable fecal testosterone (fT), glucocorticoids (fGC), estrogens (fE), and progestagen (fP) metabolite concentrations in wild baboons (Papio cynocephalus). Quadruplicate subsamples of fecal samples (n=29) collected at Amboseli National Park and its environs were subjected to four different storage conditions prior to lyophilization, in order to determine the effects of storage on subsequent steroid concentrations, as assessed by 125I radioimmunoassays. As expected, the best alternative to the "initial condition" of lyophilization at three days after collection was to freeze fecal samples at -20 degrees C for two weeks prior to lyophilization. This storage method resulted in no significant change from initial steroid concentrations for fE, fT, or fP, although fGC showed a slight but significant decline. Storage for two weeks in a charcoal refrigerator caused a mean increase in all four steroid concentrations. However, the results from this storage condition were robust in terms of practical questions asked of the data: fE and fP values still reflected pregnant versus non-pregnant states in baboon females; a fGC profile constructed by age class resembled that created from the samples from the initial condition, although slightly inflated across age classes; and there were only moderate changes in relative fT concentrations across adult males. Knowledge of the effects of storage upon each steroid analyzed within one's study is a necessary component in determining the optimal compromise for storage protocol in a particular research project.     

Non-invasive measurement of adrenocortical and gonadal activity in male and female guinea pigs (Cavia aperea f. porcellus)

Taking blood samples is a common method in biomedical and biological research using guinea pigs. However, most blood sampling techniques are complicated and highly invasive and may therefore not be appropriate for certain research topics concerning stress and reproduction. Thus, a non-invasive method to measure steroid hormones is critically needed. The aim of this study was the biological validation of corresponding enzyme immunoassays for the measurement of fecal cortisol, progesterone, estrogen, and testosterone metabolites in guinea pigs. We examined the effect of subcutaneous injections of ACTH or saline on fecal cortisol metabolites to investigate the suitability of fecal samples to monitor adrenocortical activity. Furthermore, we investigated whether fecal sex steroid metabolites accurately reflected endocrine changes observed in plasma samples during female estrous cycles and male puberty, respectively. In addition, we compared fecal testosterone metabolites of intact males, castrated males, and females to investigate the reliability of fecal samples in discriminating gonadal status of males. Concentrations of fecal cortisol metabolites were significantly increased following ACTH challenge, indicating that adrenocortical activity can be monitored via fecal samples. Secondly, in females, plasma and fecal gonadal steroids were significantly correlated in most subjects. The assay for testosterone metabolites, on the other hand, could not clearly discriminate between test groups. From these findings we conclude that fecal samples can be used for the non-invasive assessment of adrenocortical and female reproductive status in guinea pigs. Testosterone metabolism seems to be more complex and further investigations are needed to establish a more suitable assay.     

Cost-effectiveness of colorectal cancer screening: comparison of community-based flexible sigmoidoscopy with fecal occult blood testing and colonoscopy

BACKGROUND AND AIMS: To determine the cost-effectiveness of screening for colorectal cancer using flexible sigmoidoscopy once every 10 years, compared with annual and biennial rehydrated Hemoccult fecal occult blood testing and colonoscopy once every 10 years, or no screening. METHODS: A Markov model was developed in order to simulate the progression of a cohort of asymptomatic, average-risk individuals aged 55-64 years who were moving through a defined series of states towards death. The main outcome measures were: cases of colorectal cancer averted, colorectal cancer deaths averted, and cost per life-year saved. RESULTS: Colonoscopy averted the greatest number of cases of colorectal cancer (35%), followed by flexible sigmoidoscopy (25%), and annual (24%) and biennial (14%) fecal occult blood testing. Colonoscopy averted the greatest number of deaths from colorectal cancer (31%), followed by annual fecal occult blood testing (29%), flexible sigmoidoscopy (21%) and biennial fecal occult blood testing (19%). Flexible sigmoidoscopy was the most efficient in terms of cost per life-year saved (16,801 Australian dollars), followed by colonoscopy (19,285 Australian dollars), biennial (41,183 Australian dollars), and annual (46,900 Australian dollars) fecal occult blood testing. CONCLUSIONS: Flexible sigmoidoscopy and colonoscopy are cost-effective strategies for reducing the disease burden of colorectal cancer.     

Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function

We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation.     

Swine in atherosclerosis research--Development of an experimental animal model and study of the effect of dietary fats on cholesterol metabolism

The effect of saturated (beef tallow) and polyunsaturated (corn oil) fat diets on plasma cholesterol, bile flow and composition, and excretion of fecal steroids, was studied in 5 female and 6 male miniature swine. The animals were fitted with a modified Baldwin T-tube in the common bile duct for bile sampling and a catheter in the duodenum for reinfusion. Plasma cholesterol levels were increased by beef tallow and decreased by corn oil. Both fats caused an increase in the secretion of bile, biliary lipids and bile acid pool size. The increases were significant when the source of fat was corn oil. The fecal neutral steroid excretion measured in the male swine was increased by both fats. However, only the polyunsaturated fat diet caused a significant increase in the fecal acidic steroid excretion.     

Allopregnanolone and pregnanolone are produced by the human corpus luteum

Using a dispersed human luteal cell culture model, progesterone, allopregnanolone and pregnanolone release following treatment by incremental doses of human chorionic gonadotrophin (hCG) were evaluated. Corpus luteum tissues, obtained from 48 healthy women scheduled for benign surgery, were grouped according to luteal age and tissue concentration of allopregnanolone and pregnanolone was determined. The mRNA expression of 5alpha-, and 5beta-reductase and 3alpha-HSOR mRNA expressions were evaluated in corpora lutea from the late luteal phase. Allopregnanolone concentrations in corpus luteum tissue were consistently about three- to four-fold higher than pregnanolone levels. Allopregnanolone tissue concentrations significantly decreased between early- and late-luteal phase, p<0.05. When exposed to hCG, progesterone output from freshly obtained human corpora lutea cells was two- three-fold increased compared to control levels. With 0.1U/ml hCG a two-fold increase in allopregnanolone levels were noted, whereas pregnanolone levels were increased by approximately 40%. Furthermore, the mRNA of 5alpha-, 5beta-reductase and 3alpha-HSOR mRNA were all expressed in human corpus luteum. In conclusion, the neurosteroids allopregnanolone and pregnanolone are produced in the human corpus luteum and their release is stimulated by trophic hormone.     

Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK

INTRODUCTION In Germany, about 70 000 people are diagnosed with colorectal cancer each year[1]. This figure is about 1 million worldwide, with approximately 528 000 deaths from colorectal cancer each year[2]. The gold standard for the early detection of colorectal cancer is colonoscopy. However, the acceptance of this costly and invasive method is low. Only 1.7% of people entitled to colo- noscopy under the German national colorectal cancer screening program actually undergo the procedur…     

Prevention of cholesterol gallstones by lignin and lactulose in the hamster

The effect on prevention of cholesterol gallstones by a nonfermentable type of fiber, lignin, and a fermentable fiber analogue, lactulose, was studied in hamsters fed an essential fatty acid deficient diet. Control animals had a high incidence of cholesterol gallstones (21 of 24) and lithogenic bile (lithogenic index 1.08). Animals fed lignin had significantly fewer gallstones (11 of 25), improved cholesterol saturation of gallbladder bile, and increased fecal bile acid excretion. Lactulose-fed animals had significantly fewer gallstones (12 of 24) but no significant change in cholesterol saturation of gallbladder bile or in fecal bile acid excretion. Serum cholesterol concentration was reduced, however, and fecal neutral steroid excretion was increased. Gallstones were completely prevented in animals fed both lignin and lactulose (0 of 22), but gallbladder bile cholesterol saturation was not significantly different from the lignin-fed group. Gallbladder bile mucopolysaccharide concentrations did not differ among groups. Lignin appears to prevent cholesterol gallstones in this model by improving cholesterol saturation of bile. The mechanism of action of lactulose is not yet clear.     

The value of the hydrogen (H2) breath test for the diagnosis of bacterial overgrowth in gastric achlorhydria

Sixteen healthy volunteers, 23 patients with peptic disease, and 38 patients with achlorhydria were investigated with bacterial cultures from gastric juice and a hydrogen (H2) breath test after a standard meal. In acid-secreting subjects upper respiratory tract bacteria were found in 6/39. In every single achlorhydric patient gastric bacterial concentrations were above log 10 5.7/ml. Fecal flora was found in 22/38. The patient with fecal organisms were significantly older than those without (p less than 0.05). The H2 breath test revealed low postprandial carbohydrate fermentation in acid secretors and in achlorhydrics with no fecal flora. The lowest H2 production was found 90 and 120 min after the meal. In achlorhydrics with fecal organisms the mean H2 concentration at these times of measurement was elevated (p less than 0.05). Assuming that a mean H2 concentration at 90 and 120 min above 19 ppm (mean in healthy volunteers at 90 and 120 min + 2 SD) is pathological, the association of fecal bacteria in gastric juice and a "positive" H2 breath test is highly significant (P less than 0.001). Fecal bacteria in the gastric juice would indicate small-intestinal fermentation with a probability of 81%. A gastric culture negative for fecal organisms would predict a "negative" H2 breath test with a probability of 91%.     

粪便microRNAs检测用于胰腺癌筛查诊断的价值评价

目的 检测胰腺癌患者粪便microRNAs,评价其诊断价值.方法 收集29例胰腺癌患者、22例慢性胰腺炎(CP)患者以及13例健康志愿者的粪便标本,抽提粪便总RNA,应用实时定量PCR法检测各组样本miR-21、miR-155、miR-181a、miR-181b、miR-196a、miR-210的表达量,以miR-16作为内参基因.应用接受者操作特征(ROC)曲线(AUC)评估microRNAs对胰腺癌的诊断价值.结果 粪便总RNA抽提及microRNAs检测方法具有稳定及可重复性.胰腺癌组miR-181b、miR-196a、miR-210的表达量分别为2.22±0.64、2.78±0.14、5.55±0.38;CP组为1.42±0.39、3.88±0.85、5.39±0.69;对照组为0.32±0.40、1.14±0.98、4.23±0.99.胰腺癌组和CP组均较对照组显著增加(P值均＜0.05);而胰腺癌组与CP组间无显著差异.胰腺癌组对对照组的miR-181b AUC为0.745(95%CI 0.597～0.894),诊断胰腺癌的敏感性和特异性分别为84.6%和51.7%;miR-210的AUC为0.772(95%CI 0.629～0.914),对胰腺癌的诊断敏感性和特异性分别为84.6%和65.5%.两组比较差异均有统计学意义(P值均＜0.05).miR-196a对胰腺癌无诊断意义,但胰腺癌患者粪便miR-196a的表达与肿瘤直径相关(r=0.516,P=0.041).结论 粪便RNA的抽提和microRNAs检测为无创性,且具有可重复性.miR-181b和miR-210在胰腺癌患者粪便中的表达增高,有可能是胰腺癌潜在的分子标志物.     

Screening for colorectal cancer

PURPOSE: Screening for colorectal cancer using a guaiac-based fecal occult blood, or Hemoccult®, test has been demonstrated to reduce colorectal cancer mortality. However, the magnitude of effectiveness is relatively low because of poor sensitivity of the Hemoccult® test. The immunochemical fecal occult blood test has been shown to be much more sensitive than the Hemoccult® test in detecting preclinical colorectal cancer in an asymptomatic population. The purpose of this article is to discuss the validity of the immunochemical fecal occult blood test and the efficacy of a population-based screening program using the test. METHODS: Relevant articles were primarily identified through MEDLINE search. Review was focused on the studies of population screening programs with the immunochemical fecal occult blood test. RESULTS: Sensitivities for colorectal cancer calculated in the same population were reported to be 67 to 89 percent and only 33 to 37 percent for the immunochemical test and Hemoccult® test, respectively. Case-control studies and other observational studies showed that screening programs using the immunochemical fecal occult blood test by hemagglutination reaction would reduce the risk of dying of colorectal cancer by 60 percent or more for those screened annually compared with those unscreened. It was also shown that a screening strategy using the immunochemical fecal occult blood test had the best cost-effectiveness ratio among the methods available. Nearly 5 million persons are currently screened per year in Japan, yielding 0.15 to 0.2 percent colorectal cancer cases among persons with positive fecal occult blood test results. CONCLUSIONS: These results strongly suggest that a screening program with immunochemical fecal occult blood test has promising advantages in terms of effectiveness over programs with the Hemocult® test. More stress is warranted on introduction of immunochemical fecal occult blood testing as a screening test in place of the guaiac fecal occult blood test.     

Exocrine and Endocrine Pancreatic Function in 21 Patients Suffering from Autoimmune Pancreatitis before and after Steroid Treatment

Background/Aim: Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. Patients and Methods: Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 ± 16.5 years) diagnosed as having AIP between 2006 and 2008. Results: At clinical onset, fecal elastase 1 was 107 ± 126μg/g stool.Thirteen patients (62%) showed severe pancreatic insufficiency (<100 μg/g stool), 4 (19%) had mild insufficiency (100–200 μg/g stool), while 4 (19%) had normal pancreatic function (1200 μg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (<19 μg/g stool). Following steroids, fecal elastase 1 increased in all patients (237 8 193 μg/g stool) and observed levels were significantly higher than those seen before steroids (p = 0.001). Conclusions: Patients suffering from AIP display exocrine and/or endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy.     

Long-term changes in cholesterol biosynthesis and the effect of plasmapheresis therapy in a hypercholesterolemia homozygote

Synthesis of cholesterol was measured in a familial hypercholesterolemia homozygote on four occasions from age 1.1 to 9.9 years by the sterol balance technique. Both the fecal neutral steroid and fecal bile acid components of sterol balance were elevated initially. Over the decade of study, neutral steroid excretion/kg declined 61% whereas bile acid excretion/kg was unchanged. Chronic plasmapheresis therapy every two weeks for 3.4 years reduced plasma low-density lipoprotein cholesterol 54% but had little effect on the rate of cholesterol biosynthesis.     

人粪便SFRP2基因甲基化分析对结直肠癌的诊断价值

目的探讨人粪便中分泌型卷曲相关蛋白2(SFRP2)基因甲基化分析用于结直肠癌(CRC)早期诊断的可行性。方法从87例结直肠癌或良性病变的患者及24例正常对照者的粪便中分别提取DNA,采用甲基化特异性PCR(MSP)技术分析其SFRP2基因甲基化状态。结果CRC、腺瘤、增生性息肉和溃疡性结肠炎患者的SFRP2基因甲基化阳性率分别为94.2%(49/52)、52.4%(11/21)、37.5%(3/8)和16.7%(1/6)。1例正常对照SFRP2基因甲基化检测阳性。检测SFRP2基因甲基化诊断CRC及癌前病变的敏感性和特异性分别为90.5%和85.4%。结论SFRP2基因甲基化是CRC进展过程中的早期事件。粪便SFRP2基因甲基化分析可望成为CRC早期无创诊断或CRC高风险人群筛查的新途径。