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Biomedical subjects

B Krüger

Publications and source records attributed to B Krüger.

At least 19 recordsLinked to original sources
PubMed2006

Mini-incision for strictly retroperitoneal nephrectomy in living kidney donation vs flank incision.

BACKGROUND: Mini-incision donor nephrectomies (MIDNs) were established during the last decade, as an alternative to traditional open donor nephrectomy (ODN) via flank incision. In this study, we investigated intra-operative and post-operative data on outcome following MIDN in comparison with ODN data. METHODS: Data of 70 living kidney donations, performed at the University of Regensburg Medical Center since 1996, were evaluated. Donor operation was performed as either strictly retroperitoneal MIDN (n = 34) or as traditional ODN (n = 36) via flank incision. Total operation time, warm ischaemia time (WIT), perioperative pain-medication usage and creatinine levels as well as length of hospital stay, return to complete enteral nutrition and regular digestion were evaluated retrospectively. RESULTS: Total operation times were similar in MIDN, n = 34 (132 +/- 26 min) and in ODN, n = 36 (140 +/- 37 min) (P = 0.424). WIT was also similar in both: MIDN (0.9 +/- 0.4 min) and ODN (0.9 +/- 0.4 min) (P = 0.568). The requirement for post-operative opioids in morphine equivalent doses was significantly lower in MIDN (8.4 +/- 16 mg) compared with ODN (44 +/- 57 mg) (P = 0.001). Additional application of non-opioids (metamizole) (MIDN: 4.8 +/- 6.3 g, ODN: 3.4 +/- 3.9 g) and non-steroidal antirheumatic (NSAR) (diclofenac) (MIDN: 322 +/- 361 mg, ODN: 247 +/- 474 mg) revealed no significant differences between the groups. The hospital stay was 4.9 +/- 1.4 days in MIDN which was significantly shorter than that in ODN (9.3 +/- 3.3 days) (P = 0.001). Patients achieved fully independent mobility earlier in MIDN than in ODN (P = 0.934). Start of enteral nutrition with fluids was significantly quicker in MIDN (1.9 +/- 7 h) compared with ODN (12 +/- 13 h) (P = 0.05). Full enteral nutrition was accomplished significantly earlier in MIDN (1.6 +/- 0.8 days) (P = 0.023). Return to normal digestion revealed no significant differences between groups. Serum creatinine levels of all kidney donors were in the normal range (66 +/- 18 micromol/l) one day before nephrectomy, increased on day 1 after surgery (119 micromol/l +/- 31 micromol/l) and were stable on day 3 (115 micromol/l +/- 30 micromol/l) without significant differences. CONCLUSION: Strictly, retroperitoneal MIDN in living kidney donation is a fast and safe method for the procurement of a living donor graft, giving the patient a significantly shorter period of recovery, and thus is an attractive and recommendable alternative to traditional ODN procedures.

Adult↗
PubMed2006

Pretransplant calcium levels have no predictive value for delayed graft function, long-term graft function, cardiovascular events, or graft and patient survival in renal transplantation.

BACKGROUND: Disorders of calcium homeostasis are one of the most common problems in patients with end-stage renal disease (ESRD). Elevated calcium levels increase the incidence of cardiovascular mortality in ESRD patients, and appear to be a risk factor for the occurrence of delayed graft function (DGF) after kidney transplantation. Therefore, we investigated the impact of pretransplant serum calcium levels on outcomes after kidney transplantation: DGF, acute rejection, graft function, and survival, as well as the incidence of cardiovascular events. METHODS: We studied 285 patients (96.9% of all transplanted patients) who underwent their first transplantation between 1995 and 2004. Demographic data were extracted from hospital records or were documented during follow-up; serum samples were collected at the time of transplantation. RESULTS: In our cohort the incidence of DGF was 16.5% and 35.4% of acute rejection episodes (ARE). However, pretransplant calcium levels were not related to DGF or ARE in our patient cohort. Furthermore, there was no correlation between pretransplant serum calcium level with the incidence of cardiovascular events or mortality, as well as graft function or survival. CONCLUSION: In our study population pretransplant calcium levels showed no effect on DGF, ARE rate, the occurrence of cardiovascular events or death, renal graft function, or survival. Therefore, pretransplant calcium level is not a helpful marker for risk stratification at the time of transplantation.

Biomarkers↗
PubMed2006

Conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction.

BACKGROUND: Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction. METHODS: Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld. RESULTS: One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7). CONCLUSION: Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.

Adult↗
PubMed2006

Increase in renal vascular resistance after intake of cyclosporin A and tacrolimus and reversal by nitroglycerin spray: a study in patients with stable renal allograft function.

PURPOSE: Acute effects of drug administration on renal arterial resistance index (RI) are still discussed controversially. In our study we investigated the immediate effects of cyclosporin A (CyA) and tacrolimus (FK-506) on renal arterial resistance indices in patients with stable graft function after renal transplantation. Additionally we studied the effects of nitroglycerin spray on resistance indices. METHODS: RI was measured by color Doppler sonography at baseline, at 1 and 2 hours after intake of medication and 30 minutes after administration of nitroglycerin spray which followed the 2-hour measurement. 34 renal transplant recipients were examined. 16 patients received CyA, 18 patients received FK-506. Whole blood levels of calcineurin inhibitors were taken at each time point. Arterial blood pressure and heart rate were measured to assess possible systemic hemodynamic effects. RESULTS: Mean RI values increased significantly in both groups 1 hour after calcineurin inhibitor intake and remained still significantly elevated after 2 hours. There was no significant increase of mean arterial blood pressure nor was there any correlation between whole blood levels of calcineurin inhibitors and mean RI. 30 minutes after administration of nitroglycerin spray, mean RI values decreased significantly to a level even below baseline. Mean arterial blood pressure also decreased after administration of nitroglycerin. CONCLUSION: Renal RI values are markedly influenced by a recent intake of calcineurin inhibitors and vasoactive substances such as nitrates. This demonstrates the necessity of keeping standardized conditions when using RI as a tool in followup investigations after renal transplantation.

Adult↗
PubMed2005

Protein tyrosine phosphatase kappa and SHP-1 are involved in the regulation of cell-cell contacts at adherens junctions in the exocrine pancreas.

BACKGROUND: We have previously shown that cell contacts between pancreatic acinar cells dissociate early in pancreatitis and that this is a prerequisite for the development of pancreatic oedema. Here we studied the underlying mechanism. METHODS: Employing experimental caerulein induced pancreatitis in vivo and isolated pancreatic acini ex vivo, in conjunction with protein chemistry, morphology, and electron microscopy, we determined whether cell contact regulation in the pancreas requires or involves: (1) changes in cadherin-catenin protein expression, (2) tyrosine phosphorylation of adhesion proteins, or (3) alterations in the actin cytoskeleton. RESULTS: During initial cell-cell contact dissociation at adherens junctions, expression of adhesion proteins remained stable. At time points of dissociated adherens junctions, the cadherin-catenin complex was found to be tyrosine phosphorylated and internalised. The receptor type protein tyrosine phosphatase (PTP)kappa was constitutively associated with the cadherin-catenin complex at intact cell contacts whereas following the dissociation of adherens junctions, the internalised components of the cadherin-catenin complex were tyrosine phosphorylated and associated with the cytosolic PTP SHP-1. In isolated acini, inhibition of endogenous protein tyrosine phosphatases alone was sufficient to induce dissociation of adherens junctions analogous to that found with supramaximal caerulein stimulation. Dissociation of actin microfilaments had no effect on adherens junction integrity. CONCLUSIONS: These data identify tyrosine phosphorylation as the key regulator for cell contacts at adherens junctions and suggest a definitive role for the protein tyrosine phosphatases PTPkappa and SHP-1 in the regulation, maintenance, and restitution of cell adhesions in a complex epithelial organ such as the pancreas.

Actins↗
PubMed2005

Effect of genetic variation on therapy with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in dialysis patients.

INTRODUCTION: The role of interaction of polymorphisms in the Renin-Angiotensin-System (RAS) with angiotensin converting enzyme (ACE) or angiotensin receptor (AGTR1) inhibitors (RAS inhibitors) is unknown, as is the role of such therapy in end stage renal disease (ESRD) patients. METHODS: We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective survival analysis until December 2003. Blood pressure and medication was recorded at inclusion. We determined survival specific for allelic variants of the ACE (insertion/deletion), Angiotensinogen (M235T) and AGTR1 (A1166C) genes. The effect of therapy with RAS inhibitors at study inclusion was determined for the allelic variants of each gene. The primary end point was all cause mortality (ACM). RESULTS: For all polymorphisms, and for therapy with RAS inhibitors there was no significant effect on survival in the complete collective (n = 445), though there was an insignificant trend for improved survival in patients on AGTR1 antagonists. Increased ACM risk was associated with treatment with RAS inhibitors only in patients homozygous for the wild type AGTR1 1166A allele (HR 1.65, p = 0.01). For all other polymorphisms, therapy with RAS inhibitors had no significant effect on ACM, irrespective of genotype. Similar results were obtained in patients with systolic ventricular dysfunction. CONCLUSION: Our data do not show a survival advantage for type 2 diabetes hemodialysis patients receiving RAS inhibiting therapy. In addition, our data indicate that allelic variation in RAS genes and pharmacogenetic interaction with RAS inhibition does not affect mortality risk in diabetic hemodialysis patients.

Aged↗
PubMed2005

Graft function, cardiovascular risk factors, and sex hormones in renal transplant recipients on an immunosuppressive regimen of everolimus, reduced dose of cyclosporine, and basiliximab.

A prospective, randomized trial evaluated the combination of everolimus of 1.5 or 3 mg/d with steroids, basiliximab, and low-dose cyclosporine (CsA) adjusted by C2 monitoring in 256 renal transplant recipients. CsA C2 target levels, initially set at 600 ng/mL, were tapered over time posttransplant. The median serum creatinine concentrations were 130 mumol/L in both sirolimus groups (1.5 and 3 mg/d) at 6 months. Biopsy-proven acute rejection (BPAR) occurred in 13.7% and 15.1% of patients in the 1.5 and 3 mg/d groups, respectively. The incidence of BPAR was significantly higher among patients with everolimus trough levels < 3 ng/mL. Posttransplant diabetes mellitus occurred rarely, and blood pressure control appeared favorable; however, serum cholesterol levels were increased by approximately 50%, and serum triglycerides by approximately 100%. Serum testosterone concentrations increased after renal transplantation in both everolimus groups. Concentration-controlled everolimus therapy combined with low-dose CsA provides effective protection against rejection with good renal function and safety profiles.

Antibodies, Monoclonal↗
PubMed2005

Steroid withdrawal or steroid avoidance in renal transplant recipients: focus on tacrolimus-based immunosuppressive regimens.

Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.

Drug Therapy, Combination↗
PubMed2005

Cardiovascular risk estimates and risk factors in renal transplant recipients.

Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease.

Cardiovascular Diseases↗
PubMed2005

Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function.

The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5-11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3beta-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17beta-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.

3-Hydroxysteroid Dehydrogenases↗
PubMed2004

[Economic restraints shorten the length of hospital stay: thyroid operation as a model case].

INTRODUCTION: Decreasing the length of stay is a possible means of cost control in the medical system. Therefore we performed a study to test the feasibility of reducing hospital stay to 2 days after thyroid operation. METHODS: In a controlled prospective trial, 238 patients were randomly assigned to group A (2 days of stay) or group B (more than 2 days). Studied were medical standard, practicability, patient acceptance, and quality of life. RESULTS: Of those in group A, 56.6% did not leave the hospital at the scheduled 2nd day post operation. Reasons were preoperative hyperthyroidism ( P<0.011), postoperative hypocalcemia ( P<0.03), or unspecific disturbances. In group B, 28% of the patients left before the established borderline of 3-4 days, and only 35% left on the 2nd postoperative day. CONCLUSION: Reduced length of stay has no negative influence on medical standards. The quality of life of patients leaving the hospital on the 2nd postoperative day was significantly higher. Reducing hospital stay after thyroid operation to 2 postoperative days is desirable and possible without a loss in quality of care, except in case of postoperative complications or unspecific complaints.

Adult↗
PubMed2002

Contribution of the gasoline distribution cycle to volatile organic compound emissions in the metropolitan area of Mexico City.

Gasoline distribution in the metropolitan area of Mexico City (MAMC) represents an area of opportunity for the abatement of volatile organic compound (VOC) emissions. The gasoline distribution in this huge urban center encompasses several operations: (1) storage in bulk and distribution plants, (2) transportation to gasoline service stations, (3) unloading at service stations' underground tanks, and (4) gasoline dispensing. In this study, hydrocarbon (HC) emissions resulting from breathing losses in closed reservoirs, leakage, and spillage from the operations just listed were calculated using both field measurements and reported emission factors. The results show that the contribution of volatile HC emissions due to storage, distribution, and sales of gasoline is 6651 t/year, approximately 13 times higher than previously reported values. Tank truck transportation results in 53.9% of the gasoline emissions, and 31.5% of emissions are generated when loading the tank trucks. The high concentration of emissions in the gasoline transportation and loading operations by tank trucks has been ascribed to (1) highly frequent trips from distribution plant to gasoline stations, and vice versa, to cope with excessive gasoline sales per gasoline station; (2) low leakproofness of tank trucks; and (3) poor training of employees. In addition, the contribution to HC evaporative and exhaust emissions from the vehicles of the MAMC was also evaluated.

Air Pollutants↗
PubMed2001

Effect of hyperthermia on premature intracellular trypsinogen activation in the exocrine pancreas.

Hyperthermia, raising the body temperature from normal to above 40 degrees C, has been shown to prevent pancreatitis in an experimental animal model of the disease, but the underlying cellular mechanisms of this protection remain unknown. We induced controlled hyperthermia in either laboratory rats and isolated pancreatic acini or, alternatively, raised the temperature of pancreatic homogenates in vitro from 37 to 41 degrees C. In vitro controlled hyperthermia of up to 41 degrees C increased the autoactivation-induced and enterokinase-induced trypsinogen activation as well as free trypsin activity. Conversely, in whole animal studies and in living acinar cells hyperthermia reduced or abolished premature intracellular trypsinogen activation in a time- and temperature-dependent manner and this protective effect was independent of either de novo protein synthesis, interference with acinar cell signal transduction, or confirmational changes in pancreatic trypsinogen. We conclude that hyperthermia, in a manner that is independent of the synthesis of pancreatic chaperone or heat shock proteins, can directly abolish the earliest initiating event involved in the onset of pancreatitis, namely the premature and intracellular activation of digestive zymogens.

Animals↗
PubMed2000

The role of cysteine proteases in intracellular pancreatic serine protease activation.

Autodigestion by proteolytic enzymes is thought to represent the critical mechanism by which acute pancreatitis is initiated. Where and why pancreatic proteases, which are physiologically stored and secreted as inactive precursor zymogens, are activated within the pancreas has remained controversial. Here we present data which indicate that: the lysosomal protease cathepsin B can activate trypsinogen in vitro in a manner that is similar to trypsinogen activation by enterokinase; that cathepsin B colocalizes with trypsinogen in the secretory compartment of the rat pancreas and of the human pancreas; that trypsinogen activation begins in a secretory compartment that is distinct from mature zymogen granules; and that the inhibition of cathepsin B can either increase or decrease premature trypsinogen activation depending on the concentration of the inhibitor, its specificity and its site of action in the pancreatic acinar cell. These observations elucidate some of the complex relations between cysteine and serine proteases in the pancreas with respect to their mechanisms of activation, their subcellular sites of action, and their possible role in the onset of pancreatitis.

Acute Disease↗
PubMed2000

Thiazolidinedione-induced activation of the transcription factor peroxisome proliferator-activated receptor gamma in cells adjacent to the murine skeletal muscle: implications for fibroblast functions.

Nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) is the target of antidiabetogenic thiazolidinediones (TZD). However, recent studies failed to show that TZD has an effect in vitro on insulin-regulated glucose uptake in skeletal muscles, the major site of glucose disposal. The potential effects of TZD on cells adjacent to skeletal muscles are not well characterized but may be involved in TZD's actions. Hence, we studied these cells from mice treated with the carrier and with the TZD ciglitazone (9 nmol/g body weight). The cells were typified by lipid enrichment (floating adipocytes and macrophages), by the ectopic expression of cellular fibronectin (fibroblasts), fibronectin and PPARgamma (preadipocytes), PPARgamma and CD11b/Mac-1 (active macrophages) as revealed by flow cytometry and immunoblotting. The glucose transporter 4 proteins (GLUT4) and the uptake of glucose and long-chain fatty acids (LCFA) were determined flow cytometrically using fluorescent derivatives of glucose (NBDG) and LCFA (C16-Bodipy). The expression of tumor necrosis factor alpha (TNFalpha) in CD11b/Mac-1-positive and CD11b/Mac-1-negative cells separated by magnetic immunobeads was analyzed. The results showed that TZD treatment upregulated GLUT4 expression, and increased insulin-regulated NBDG uptake and C16-Bodipy binding and influx, at the same time as increasing the quantity of PPARgamma-expressing fibroblasts; this indicates the development of the preadipocyte phenotype. In contrast, TZD lowered the number of adipocytes (0.6-fold compared to the carrier-treated control) perhaps through an action of TNFalpha from CD11b- and PPARgamma-expressing macrophages. The data suggest that the regulatory effects of TZD on energy homeostasis involve two major targets: the PPARgamma-positive fibroblasts whose adipogenic program is promoted, and CD11b-PPARgamma-expressing macrophages which become cytotoxic and fibrogenic because of the effects of TNFalpha on neighboring adipocytes and fibroblasts, respectively.

Adipocytes↗
PubMed2000

The role of intracellular calcium signaling in premature protease activation and the onset of pancreatitis.

The exocrine pancreas synthesizes and secretes large amounts of digestive proteases as inactive precursor zymogens. Under physiological conditions a variety of cellular defense mechanisms protect the pancreatic acinar cell against a premature and intracellular activation of these zymogens. When these defenses fail, pancreatic autodigestion is initiated and acute pancreatitis can develop. A number of experimental observations suggest that extra- as well as intracellular calcium concentrations play an important part in the initiation of pancreatic protease activation, but the intracellular signaling events that regulate this process are unknown. Using a model system in which we used pancreatic acini (freshly prepared functional units of living acinar cells), we were able to simulate the conditions found during experimental pancreatitis in rodents. By means of a cell permeant fluorescent trypsin substrate we could demonstrate in these acini that premature protease activation is initiated at the apical acinar cell pole and occurs only in the presence of secretagogue concentrations that exceed those required for a maximum secretory response. By combining this technique with fluorescence ratio imaging for the Ca(2+)-sensitive dye fura-2, we could further show that this protease activation is highly dependent on the spatial as well as the temporal distribution of the corresponding Ca(2+) release from stores within the same subcellular compartment and that it is not propagated to neighboring acinar cells.

Animals↗
PubMed2000

Contribution of LPG-derived emissions to air pollution in the metropolitan area of Guadalajara City.

Measurements of hydrocarbon (HC) emissions generated by the use of liquefied petroleum gas (LPG) in the metropolitan area of Guadalajara City (MAG) are presented in this work. Based on measurements in the course of distribution, handling, and consumption, an estimated 4407 tons/yr are released into the atmosphere. The three most important contributors to LPG emissions were refilling of LPG-fueled vehicles and commercial and domestic consumption. The MAG shows a different contribution pattern of LPG emission sources compared with that of the metropolitan area of Mexico City (MAMC). These results show that each megacity has different sources of emissions, which provides more accurate strategies in the handling procedures for LPG to decrease the impact in O3 levels. This work represents the first evaluation performed in Guadalajara City, based on current measurements, of the LPG contribution to polluting emissions.

Air Pollution↗