Eukaryotic inhibitors or activators elicit responses to chemosensory compounds by ruminal isotrichid and entodiniomorphid protozoa.

Our objectives were to evaluate potential signaling pathways regulating rumen protozoal chemotaxis using eukaryotic inhibitors potentially coordinated with phagocytosis as assessed by fluorescent bead uptake kinetics. Wortmannin (inhibitor of phosphoinositide 3-kinase), insulin, genistein (purported inhibitor of a receptor tyrosine kinase), U73122 (inhibitor of phospholipase C), and sodium nitroprusside (Snp, nitric oxide generator, activating protein kinase G) were preincubated with mixed ruminal protozoa for 3h before assessing uptake of fluorescent beads and chemosensory behavior to glucose, peptides, and their combination; peptides were also combined with guanosine triphosphate (GTP; a chemorepellent). Entodiniomorphids were chemoattracted to both glucose and peptides, but chemoattraction to glucose was increased by Snp and wortmannin without effect on chemoattraction to peptides. Rate of fluorescent bead uptake by an Entodinium caudatum culture decreased when beads were added simultaneously with feeding and incubated with wortmannin (statistical interaction). Wortmannin also decreased the proportion of mixed entodiniomorphids consuming beads. Isotrichid protozoa exhibited greater chemotaxis to glucose but, compared with entodiniomorphids, were chemorepelled to peptides. Wortmannin increased chemotaxis by entodiniomorphids but decreased chemotaxis to glucose by isotrichids. Motility assays documented that Snp and wortmannin decreased net swimming speed (distance among 2 points per second) but not total swimming speed (including turns) by entodiniomorphids. Wortmannin decreased both net and total swimming behavior in isotrichids. Results mechanistically explain the isotrichid migratory ecology to rapidly take up newly ingested sugars and subsequent sedimentation back to the ventral reticulorumen. In contrast, entodiniomorphids apparently integrate cellular motility with feeding behavior to consume small particulates and thereby stay associated and pass with the degradable fraction of rumen particulates. These results extend findings from aerobic ciliate models to explain how rumen protozoa have adapted physiology for their specific ecological niches.

[Monitoring of glucose concentration in critical patients, comparing arterial blood glucose concentrations and interstitial glucose concentration measured by microdialysis technique]. / Monitorování glykemie u kriticky nemocných pacientu: srovnání arteriálních a intersticiálníh hladin glukózy merených pomocí mikrodialýzy tukové tkáne.

INTRODUCTION: Recent studies have shown that normalization of blood glucose in critically ill patients by intensive insulin therapy significantly decreases their mortality and morbidity. The aim of our study was to compare interstitial glucose concentrations in subcutaneous adipose tissue (measured by microdialysis technique) and arterial blood glucose concentrations to test the suitability of subcutaneous adipose tissue for long-term placement of biosensors for glucose measurement in critically ill patients. PATIENTS AND METHODS: 20 patients (16 men and 4 women) after cardiac surgery hospitalized at postoperative intensive care unit were included into the study. Mean age was 68 +/- 10 years, BMI was 28.3 +/- 3.9 year. Only patients with glycemia higher than 6.7 mmol/l at a time of admission to the ICU were included. Samples for measurement of interstitial glucose concentrations were collected in 60 minutes intervals during 48 hours using microdialysis of the subcutaneous adipose tissue. Perfusion fluid was 5% mannitol, perfusion rate was 1 microl/min. Arterial blood glucose concentration was measured in 60 minutes intervals, absolute concentrations of interstitial glucose were calculated using ionic reference technique. RESULTS: Mean arterial glucose concentration during the study was 6.7 +/- 0.56 mmol/l, absolute concentration of glucose in interstitial fluid was 3.55 +/- 0.58 mmol/l. Mean correlation coefficient between arterial and interstitial concentrations was 0.77 +/- 0.15. CONCLUSION: Our study demonstrated good correlation between interstitial glucose concentrations in subcutaneous adipose tissue and arterial blood glucose concentrations in post-cardiac surgery patients. Further studies are needed to evaluate this relationship in patients with more severely disturbed perfusion of subcutaneous adipose tissue.

Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus.

BACKGROUND: In short acting insulin analogues the dissociation of hexamers is facilitated, achieving peak plasma concentrations about twice as high and within approximately half the time compared to regular human insulin. According to these properties this profile resembles the shape of non-diabetic patients more than that of regular human insulins. Despite this theoretical superiority of short acting insulin analogues over regular human insulin, the risk-benefit ratio of short acting insulin analogues in the treatment of diabetic patients is still unclear. OBJECTIVES: To assess the effect of treatment with short acting insulin analogues versus regular human insulin. SEARCH STRATEGY: A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on short acting insulin analogues versus regular human insulin was performed using the Cochrane Library (issue 4, 2003), MEDLINE and EMBASE. Date of last search was December 2003. SELECTION CRITERIA: We included randomised controlled trials with diabetic patients of all ages that compared short acting insulin analogues to regular human insulin. Intervention duration had to be at least 4 weeks. DATA COLLECTION AND ANALYSIS: Trial selection as well as evaluation of study quality was done by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and Jadad. MAIN RESULTS: Altogether 7933 participants took part in 42 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was estimated to be -0.1% (95% CI: -0.2% to -0.1%) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was estimated to be 0.0% (95% CI: -0.1% to 0.1%). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3% to -0.1%) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII) whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.2% to -0.0%). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.2 to 0.9) and -0.2 (95%CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetic patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 20.3) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 37.2) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.6) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 2.8) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications. REVIEWERS' CONCLUSIONS: Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. Due to fears of potentially carcinogenic and proliferative effects, most studies to date have excluded patients with advanced diabetic complications. For safety purposes, we need a long-term follow-up of large numbers of patients who use short acting insulin analogues. Furthermore, we need well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus.

BACKGROUND: In short acting insulin analogues the dissociation of hexamers is facilitated, achieving peak plasma concentrations about twice as high and within approximately half the time compared to regular human insulin. According to these properties this profile resembles the shape of non-diabetic patients more than that of regular human insulins. Despite this theoretical superiority of short acting insulin analogues over regular human insulin, the risk-benefit ratio of short acting insulin analogues in the treatment of diabetic patients is still unclear. OBJECTIVES: To assess the effect of treatment with short acting insulin analogues versus regular human insulin. SEARCH STRATEGY: A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on short acting insulin analogues versus regular human insulin was performed using the Cochrane Library (issue 1, 2003), MEDLINE and EMBASE. Date of last search was December 2003. SELECTION CRITERIA: We included randomised controlled trials with diabetic patients of all ages that compared short acting insulin analogues to regular human insulin. Intervention duration had to be at least 4 weeks. DATA COLLECTION AND ANALYSIS: Trial selection as well as evaluation of study quality was done by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and Jadad. MAIN RESULTS: Altogether 7933 participants took part in 42 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was estimated to be -0.1% (95% CI: -0.2% to -0.1%) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was estimated to be 0.0% (95% CI: -0.1% to 0.1%). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3% to -0.1%) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII) whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.2% to -0.0%). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.2 to 0.9) and -0.2 (95%CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetic patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 20.3) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 37.2) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.6) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 2.8) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications. REVIEWERS' CONCLUSIONS: Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. Due to fears of potentially carcinogenic and proliferative effects, most studies to date have excluded patients with advanced diabetic complications. For safety purposes, we need a long-term follow-up of large numbers of patients who use short acting insulin analogues. Furthermore, we need well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Pseudomonas sp. strain KC represents a new genomovar within Pseudomonas stutzeri.

Pseudomonas sp. strain KC (= ATCC 55595 = DSM 7136) is a denitrifying aquifer isolate that produces and secretes pyridine-2,6-bis(thiocarboxylate) (PDTC), a chelating agent that fortuitously transforms carbon tetrachloride without producing chloroform. Although KC has been used successfully for full-scale bioremediation of carbon tetrachloride, its taxonomy has proven difficult to resolve, as it retains properties of both Pseudomonas stutzeri and Pseudomonas putida. In the present work, a polyphasic approach was used to conclude that strain KC represents a new genomovar (genomovar 9) within the species P. stutzeri.

Squamous cell carcinoma of the penis. Analysis of 24 cases.

The authors evaluated retrospectively 24 cases of spinocellular carcinoma of the penis, trying to detect aetiological carcinogenic factors of the disease. Phimosis persisting since childhood was reported by ten men, whereby in five of them circumcision was performed during puberty. The duration of symptoms up to the time of biopsy and histological verification of differentiated spinocellular carcinoma of the penis varied from one month to thirteen years. Eight patients (33.3%) belonged to category T1, 8 (33.3%) to T2 and 8 (33.3%) to T3. Fifteen tumours (62.5%) were G1, 5 (20.8%) G2 and 4 (16.7%) G3. In 5 men print cytology was negative.

[Developmental trends in pathology]. / Trendy rozvoja patológie.

The paper calls attention to the main problems of pathology in Czechoslovakia. There is a need of performance standards for quality assessment and for the health insurance.

[Classification of the lung conditions in cases of perinatal death]. / Klassifikation der Lungenbefunde bei perinatalen Todesfällen.

Comparability of morphological lung findings depends on the greatest possible consistency in assessment and verbal definition. It is for that purpose that a classification of perinatal pulmonary morphology is proposed, based on latest knowledge in foetal and paediatric pathology and established with due consideration of findings from clinical and physiological research as well as of the author's own experience. The findings have been subdivided into five main groups, each of them with several sub-groups, and have been pathomorphologically so characterised that the new classification can be easily used in prosector practice.

Adrenal function in the carcinoid syndrome: effects of the serotonin antagonist cyproheptadine.

Results of evaluations of adrenal function in 11 patients with carcinoid tumors are presented. Nine patients had tumors that made and secreted serotonin resulting in elevated 5-hydroxyindoleacetic acid (5-HIAA), elevated serum serotonin, and the carinoid syndrome; while two patients had tumors that did not make serotonin and that did not cause elevated 5-HIAA excretion or elevated serum serotonin. All of the patients had normal 24-hr 17-hydroxycorticosteroid excretion. In the group of patients with tumors actively secreting serotonin, the correlation between 17-hydroxycorticosteroid and 5-HIAA excretion (r = 0.44) was not significant. Six of these patients pretreated with cyproheptadine (CYPRO), a serotonin antagonist, experienced a 36% mean decrease in 17-hydroxycorticosteroid excretion, a finding that was not present when three of them were treated with triprolidine (TPRO), an antihistamine. Serum cortisol at 8 a.m. was normal in all patients except two whose values were mildly elevated, and these two patients showed evidence of suppression of ACTH secretion secondary to dexamethasone treatment. There was a significant positive correlation between serum-cortisol concentrations and 5-HIAA excretions (r = 0.73, p less than .05). Normal diurnal variation was present in six patients in whom it was determined. The serum-cortisol response to insulin-induced hypoglycemia in six patients who had carcinoid tumors actively secreting serotonin was not statistically different from that of 12 normal volunteers. Comparisons between these two groups were difficult because the carcinoid patients' fall in blood sugar was 50%, whereas that of the control group was to 38% of the fasting glucose concentration. Six patients with actively secreting carcinoid tumors responded to standard metyrapone testing with a mean increment of 22.8 +/- 2.5 mg/day in 17-hydroxycorticosteroids. This response was statistically different from the increment of 13.8 +/- 5.3 mg/day in 17-hydroxycorticosteroid excretion found in 34 age-matched hospitalized control patients. When the tests were repeated in four of the patients with carcinoid tumors after pretreatment with CYPRO, the increment in 17-hydroxycorticosteroid excretion was reduced well below the mean increment of the control group. Peak serum 11-deoxycortisol (Compound S) values during the test were also reduced. This decrease in the metyrapone response after CYPRO pretreatment was not due to changed peripheral cortisol metabolism, altered adrenal responsiveness to ACTH, interference with recovery of 17-hydroxysteroids by the Porter-Silber reaction, altered metyrapone metabolism, or reduced renal clearance of Compound S. These changes in adrenal response to metyrapone were not seen when the patients were pretreated with TPRO. Our data suggest that the alterations in adrenal function in our patients may be related to elevated serum serotonin. If CYPRO acts by antagonizing serotonin, these data may give support to the idea of serotoninergic control of cortisol secretion.