A detailed regimen of isotretinoin for the successful treatment of severe keratosis pilaris.

Although a well-known recommended treatment option, there are currently no studies that describe the detailed regimen of isotretinoin for the treatment of primary keratosis pilaris. Based on previous studies involving other hyperkeratotic disorders, this report describes a safe and effective treatment course of isotretinoin for severe keratosis pilaris.

DUSP4 appears to be a highly localized endogenous inhibitor of epileptic signaling in human neocortex.

BACKGROUND: We previously identified the Mitogen Activated Protein Kinase (MAPK) pathway as focally upregulated in brain regions with high epileptic activity and showed that inhibition of MAPK signaling reduces epileptic spiking in an animal model. Here we examined how activators and inhibitors of the MAPK pathway are expressed in human epileptic cortex and how these could contribute to the localization of epileptic signaling. METHODS: We localized gene and protein expression in human epileptic neocortical tissues based on epileptic activities from 20 patients based on long-term intracranial recordings. Follow-up mechanistic studies by depolarization of human Sh-SY5Y cell line were used to model epileptic activity in the human brain. RESULTS: A clustering algorithm of differentially expressed genes identified a unique gene expression cluster distinct from other MAPK genes. Within this cluster was dual specificity phosphatase 4 (DUSP4), a potent MAPK inhibitor. In situ hybridization studies revealed focal patches of DUSP4 mRNA in layer 2/3 brain regions associated with a dramatic reduction in MAPK signaling genes. In vitro depolarization led to the rapid and transient induction of DUSP4 protein, which, in turn, reduced MAPK activity. Activity-dependent induction of DUSP4 protein was transient and required MAPK signaling. Human epileptic brain regions with lower epileptic activity had lower MAPK activity and higher DUSP4 protein levels. DISCUSSION: DUSP4 is a highly localized, endogenous feedback inhibitor of pro-epileptogenic MAPK signaling in the human epileptic brain. Increasing DUSP4 expression could therefore be a novel therapeutic approach to prevent the development and spread of epileptic circuits. SIGNIFICANCE STATEMENT: Epilepsy is a chronic debilitating disease. Once it develops, epileptic circuits often persist throughout life. Fortunately, in focal forms of epilepsy, these circuits can remain highly localized and are amenable to surgical resections, suggesting that endogenous mechanisms restrict their spread to other brain regions. Using a high-throughput genomic analysis of human epileptic brain regions, we identified DUSP4 as an activity-dependent inhibitor of MAPK signaling expressed in focal patches surrounding human neocortical epileptic brain regions. Our results suggest that DUSP4, through local inhibition of MAPK signaling, acts as an endogenous, spatially segregated safety mechanism to prevent the spread of epileptic activity. Augmenting DUSP4 expression could be a novel disease-modifying approach to prevent or treat human epilepsy.

Active matrix metalloproteinase-8 and periodontal bacteria depending on periodontal status in patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: The aim of this clinical cross-sectional study was to determine the level of active matrix metalloproteinase-8 (aMMP-8) and periodontal pathogenic bacteria in gingival crevicular fluid in patients with rheumatoid arthritis (RA) with varying periodontal conditions. MATERIAL AND METHODS: In total, 103 patients with RA and 104 healthy controls (HC) were included. The assessment of periodontal status included periodontal probing depth, bleeding on probing and clinical attachment loss. Periodontal disease was classified as healthy/mild, moderate or severe. For the determination of aMMP-8 levels using enzyme-linked immunosorbent assay and periodontal pathogenic bacteria using polymerase chain reaction, samples of gingival crevicular fluid were taken from the deepest gingival pockets. The statistical analyses used included a Mann-Whitney U-test, a chi-squared test or a Fisher's exact test, and the significance level was set at α = 5%. RESULTS: We found that 65% of patients with RA and 79% of HC had moderate to severe periodontal disease (p = 0.02). The prevalence of periodontal pathogens was almost equal (p > 0.05). Furthermore, depending on periodontal disease severity only minor differences in bacterial prevalence were detected. With increasing severity of periodontal disease, higher aMMP-8 levels were observed. Accordingly, a significant difference in patients with moderate periodontal disease (RA: 15.3 ± 13.8; HC: 9.1 ± 9.1; p ≤ 0.01) and severe periodontal disease (RA: 21.7 ± 13.3; HC: 13.1 ± 8.6; p = 0.07) was detected, with a greater tendency in the latter group. CONCLUSION: The increased aMMP-8 levels in the RA group indicate that the presence of RA appears to have an influence on the host response at a comparable level of bacterial load and periodontal disease severity.

Kinetic limitation of chemical ordering in Bi2Te3-x Se x layers grown by molecular beam epitaxy.

We study the chemical ordering in Bi2Te3-x Se x grown by molecular beam epitaxy on Si substrates. We produce films in the full composition range from x = 0 to 3, and determine their material properties using energy dispersive x-ray spectroscopy, x-ray diffraction and Raman spectroscopy. By fitting the parameters of a kinetic growth model to these results, we obtain a consistent description of growth at a microscopic level. Our main finding is that despite the incorporation of Se in the central layer being much more probable than that of Te, the formation of a fully ordered Te-Bi-Se-Bi-Te layer is prevented by kinetic of the growth process. Indeed, the Se concentration in the central layer of Bi2Te2Se1 reaches a maximum of only ≈ 75% even under ideal growth conditions. A second finding of our work is that the intensity ratio of the 0 0 12 and 0 0 6 x-ray reflections serves as an experimentally accessible quantitative measure of the degree of ordering in these films.

Elemental distribution, solute solubility and defect free volume in nanocrystalline restricted-equilibrium Cu-Ag alloys.

In this article we study the elemental distribution and solute solubility in nanocrystalline alloys of immiscible components near restricted equilibrium for the case of the binary Cu-Ag system. As predicted from thermodynamic considerations, a grain boundary segregated monophase alloy is observed in the annealed mechanically alloyed state for low Ag content by using atom probe tomography. From the detected Ag solute grain boundary enrichment the segregation free enthalpy is estimated to range between -25 and -49 kJ mol(-1) following the McLean equation, in agreement with values reported for coarse-grained Cu-Ag. The extension of the alloying range is described by a two-domain thermodynamic model that considers the excess free volume in the grain boundaries and the strain in the grain interior on the basis of the universal equation of state at negative pressure. To access the grain boundary volumetric strain experimentally, a method based on a combination of density measurements and microscopical quantification of closed pore areas is presented. Moreover, we apply x-ray diffraction line broadening analysis to determine the local strain amplitude, which yields a root-mean-square microstrain of ~0.3% for a grain size of ~30 nm. It is shown that the grain boundary free volume represents the major origin for the global solubility enhancement in nanocrystalline Cu-Ag at 503 K.

The RAGE pathway in inflammatory myopathies and limb girdle muscular dystrophy.

Oxidative stress and nuclear factor-kappaB (NF-kappaB) activation are linked to the pathogenesis of many metabolic, degenerative, and chronic inflammatory diseases. Activation of the receptor for advanced glycation end products (RAGE) by its specific ligand N(epsilon)-carboxymethyllysine (CML) results in the activation of NF-kappaB and the production of proinflammatory cytokines. To determine whether engagement of RAGE contributes to the pathogenesis of inflammatory myopathies, we performed immunohistochemical studies on the presence of CML-modified proteins, RAGE and activated NF-kappaB in muscle biopsies of patients with polymyositis (PM, n=10), dermatomyositis (DM, n=10), limb girdle muscular dystrophy (LGMD, n=10) and in 10 controls with normal muscle biopsy results. In inflammatory myopathies CML, RAGE and NF-kappaB were detected in mononuclear cells and in regenerating muscle fibers. CML, NF-kappaB and, to a lesser extent, RAGE were also found in degenerating muscle fibers, but colocalization of CML, RAGE and NF-kappaB was only seen in infiltrating mononuclear cells and regenerating muscle fibers. Immunofluorescence double labeling demonstrated an expression of CML, RAGE and NF-kappaB in CD4-, CD8-, CD22- and CD68-positive mononuclear cells. Western blot analysis showed an increased immunoreactivity for CML-modified proteins in PM and DM. In LGMD, CML, RAGE and NF-kappaB were found in regenerating muscle fibers and less frequently in degenerating muscle fibers, and with lower staining intensities than in inflammatory myopathies. Our data suggests that the CML-RAGE-NF-kappaB pathway is an evident proinflammatory pathomechanism in mononuclear effector cells in PM and DM. RAGE-mediated NF-kappaB activation may be involved in muscle fiber regeneration in inflammatory myopathies and LGMD.

Influence of vagus nerve stimulation on histamine-induced itching.

OBJECTIVE: To investigate whether vagus nerve stimulation (VNS) reduces pruritus in humans. BACKGROUND: Recently, it has been shown that VNS has antinociceptive and antidepressant effects in humans. METHODS: Eleven patients were investigated before (baseline) and during chronic VNS treatment. The experiments were performed at two different stimulation intensities: 2 to 5 days after implantation at a low stimulation intensity (mean intensity 0.7 +/- 0.2 mA, second session) and after 8 to 14 weeks of VNS therapy (mean intensity 1.4 +/- 0.3 mA, third session). Twelve healthy age- and sex-matched subjects were investigated using the same experimental protocol. Itch was induced by histamine-iontophoresis and quantified on a visual analogue scale (VAS). Histamine-induced flare was quantified using laser-Doppler flowmetry. RESULTS: Itch was reduced by VNS from 24 +/- 8% VAS at baseline to 15 +/- 5% VAS at second session, and 19 +/- 8% VAS at third session (p < 0.05 multivariate analysis of variance). In the control group, itch remained unaltered in all three sessions (26 +/- 5% at baseline, 23 +/- 5% in the second session, and 25 +/- 5% in the third session, not significant). The flare was unaltered in both patients and control subjects. CONCLUSIONS: VNS may suppress pruritus in humans.

Sex differences and lateral asymmetry in heart rate modulation in patients with temporal lobe epilepsy.

This study was designed to study the influence of gender and lateral hemispheric asymmetry on heart rate modulation during temporal lobe seizures. Heart rate was recorded during complex partial seizures in 10 female and 11 male patients (12 with a right temporal lobe focus, nine with a left focus), with simultaneous video monitoring and bilateral subdural electrode placement. Heart rate changes were analysed during the seizure, at a time when the epileptic activity was restricted to one hemisphere. In this analysed interval, the heart rate of patients with a right temporal lobe focus showed a significant increase, from 73.5 to 91.0 beats/min (F = 10.7, df = 2.3/27, p < 0.001), while the heart rate of patients with a left sided focus only increased slightly, from 77.0 to 82.5 beats/min (NS). An effect of sex was demonstrated, in that the influence of focus laterality could only be shown in male patients (F = 14.24, df = 2.58/27, p < 0.001). These results confirm the right hemispheric lateralisation of sympathetic cardiac control in male patients.

N(epsilon)-Carboxymethyllysine in diabetic and non-diabetic polyneuropathies.

Increased oxidative stress and advanced glycosylation are important factors in the development of diabetic neuropathy. In non-diabetic neuropathies their influence has not been investigated in detail so far. We studied the localisation of N(epsilon)-carboxymethyllysine (CML) - a biomarker for oxidative stress - by immunohistochemistry in sural nerve biopsies of 31 patients with different polyneuropathies [diabetic polyneuropathy (n=5), alcohol-associated polyneuropathy (n=4), vitamin B12-deficient polyneuropathy (n=6), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=6), vasculitic neuropathy (n=6), Charcot-Marie-Tooth disease type I (CMT I) (n=4)] and 4 normal controls. CML was detected in the perineurium of patients with diabetic, alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathies. Epineurial, perineurial and endoneurial vessels were CML positive in diabetic, vitamin B12-deficient and vasculitic polyneuropathies. CML was also found in mononuclear inflammatory cells in vasculitic neuropathy. In CIDP and normal controls there was only marginal perineurial CML deposition in 2/6 and 1/4 cases. In CMT I no CML was detected. Immunohistochemical results were confirmed by immunoblot. Our data suggest a role of oxidative stress in the pathogenesis not only of diabetic but also of alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathies. It may be a minor pathogenetic factor in CIDP and may not be involved in CMT I. Underlying causes for increased oxidative stress may be an elevated production of reactive oxygen species and an impairment of antioxidative defences. Therefore, an antioxidative treatment should be considered in alcohol-associated, vitamin B12-deficient and vasculitic polyneuropathy.

Therapeutic intensive seizure analysis (TISA) in presurgical evaluation of Losigamone.

OBJECTIVE: The new method TISA was used to evaluate Losigamone efficacy. METHODS: Sixteen patients with pharmacoresistant partial seizures undergoing presurgical evaluation were randomized in this double-blind, placebo-controlled, parallel-group Losigamone monotherapy study under continuous video-EEG monitoring. Duration (in s, of each seizure and each ictal sign), intensity (grade zero to three), N/24h (number of seizures and ictal signs per 24 h), D/24h (seconds per 24 h covered by seizures and ictal signs) and seizure free intervals were recorded. RESULTS: A total of 246 seizures were intensively analyzed. The duration and intensity of all seizures improved more in the active treatment group than in the placebo group. There was a statistically significant superiority in the duration of the seizure free interval in the Losigamone group. Ictal signs such as oro-alimentary automatisms and fumbling were improved during Losigamone treatment. CONCLUSION: Losigamone has a preferred inhibitory effect on propagated epileptic activity. TISA is a sensitive method for evaluation of the selective effects of AEDs.

[Vagus nerve stimulation - a new option for the treatment of chronic pain syndromes?]. / Vagusstimulation - Eine Behandlungsoption für chronische Schmerzen?

Electrical stimulation of the vagal nerve (VNS) has become an established method for treating medically refractory epilepsies. From animal experiments it is well known that depending on the stimulation intensity VNS can elicit both inhibition and facilitation of nociception. Recent physiologic investigations demonstrated a similar influence of VNS on pain perception in patients treated by chronic VNS. However, in humans, a more marked effect was shown for the pain inhibition which is probably mediated by neurobiochemical mechanisms. These findings are discussed in consideration of the physiologic mechanisms underlying the modulation of pain and seizures by VNS known from animal studies. First reports of attenuation of chronic pain by VNS indicate that the method might be an option for pain treatment in the future.

Left vagus nerve stimulation suppresses experimentally induced pain.

OBJECTIVE: To test whether electric stimulation of the vagus nerve has an antinociceptive effect in humans. BACKGROUND: In a variety of animal studies, vagus nerve stimulation was shown to inhibit nociceptive behavior as well as electric responses of spinal nociceptive neurons. In humans, chronic left vagus nerve stimulation is used to treat pharmacologically refractory epilepsy. METHODS: The authors investigated experimental pain in 10 patients with seizures before and twice after implantation of a vagus nerve stimulator by using different controlled stimuli, including noxious heat, tonic pressure, and short impact. Pain was quantified on a visual analogue scale. Twelve nonepileptic age- and gender-matched individuals served as control subjects. RESULTS: Vagus nerve stimulation reduced increasing pain associated with trains of five consecutive stimuli at 1.5-second intervals ("wind-up"; p < 0.001). In a similar manner, pain on tonic pressure was reduced by vagus nerve stimulation (p < 0.03). Pain associated with single-impact stimuli as well as heat pain thresholds were unaltered under vagus nerve stimulation. Thus, vagus nerve stimulation led to pain relief predominantly in experimental procedures in which pain magnitude was amplified by central processing. The antinociceptive effect was independent of the acute on-off cycles of vagus nerve stimulation. CONCLUSIONS: Vagus nerve stimulation is effective in reducing pain in humans. In humans, the antinociceptive effect might rely on central inhibition rather than alterations of peripheral nociceptive mechanisms. These results indicate a promising, potential future role of vagus nerve stimulation in pain treatment.

[Lassa fever]. / Lassa-Fieber.

UNLABELLED: A 22-year-old female German student was admitted with fever of unknown origin for 5 days to the hospital of her hometown immediately after returning from a 7-week journey under simple conditions through 4 West African countries. After exclusion of malaria and typhoid and nonrespondence to antibiosis, she was transferred on the 4th day to the Department of Tropical Medicine in Würzburg. After the clinical assumption of Lassa fever, the virus was confirmed by PCR within 3 hours (Bernhard Nocht Institute, Hamburg) on the 10th day of her illness. The assumption was based on travel history, continuous fever, cough, pharyngitis, thoracic pain, and exclusion of other acute infections. From the beginning, the patient was cared for with barrier nursing and after diagnosis under strict isolation in an intensive care unit reserved for her alone by a team of doctors and nurses specialized in tropical medicine and intensive care. The staff was protected through isolation suits with filters. Monitoring and therapy entailed all methods of intensive care and intravenous administration of ribavirin 16 mg/kg body weight = 900 mg every 6 hours. The patient died on the 14th day of her illness in a volume deficiency shock due to uncontrollable heavy hemorrhage from all organs including the skin, a so-called "leakage syndrome". CONCLUSION: Conclusions are drawn regarding training in tropical medicine, diagnostics of highly contagious infections, intensive care of patients affected with them under isolation, contact tracing, psychological crisis intervention for personnel, media information, care of the infectious corpse and disposal of infectious waste.

[Temporal lobe epilepsy: effect of focus side on the autonomic regulation of heart rate?]. / Temporallappenepilepsien. Einfluss der Fokusseite auf die autonome Regulation der Herzfrequenz?

Epileptic activity can modulate reactions of the autonomic nervous system. Although there is some evidence of a differential left/right hemispheric influence on the cardiovascular system, diverse investigations have shown controversial results. In our study, complex partial seizures of patients with temporal lobe epilepsy were recorded using subdural electrodes, thus providing reliable information on the focus side. We analyzed the preictal and ictal heart rates of 27 patients, 16 revealing right and 11 revealing left temporal foci. During the seizures, both groups showed a significant increase in heart rate. Preictal tachycardia was only significant in the right focus group, whereas no significant change in heart rates could be detected in the left focus group. Our results confirm a right hemispheric lateralization of sympathetic cardiac control.

Experimental silicosis: a shift to a preferential IFN-gamma-based Th1 response in thoracic lymph nodes.

In chronic silicosis, mechanisms leading to lymphocyte activation are still poorly understood, although it is well known that not only the lung but also the draining lymph nodes are affected. In the present study, we investigated T-cell activation by analysis of cytokine expression in the enlarged thoracic lymph nodes of rats 2 mo after an 8-day silica aerosol exposure. In the case of helper T cell (Th) type 1 cytokines, we found a significant increase in interferon (IFN)-gamma mRNA expression, whereas interleukin (IL)-2 expression remained unchanged. In contrast, gene transcription for the Th2-type cytokines IL-4 and IL-10 was diminished. In addition, with use of an in vitro lymphocyte-macrophage coculture system, an enhanced IFN-gamma and a reduced IL-10 release were shown with cells from silicotic animals. With regard to IFN-gamma-inducing cytokines, we observed enhanced IL-12 mRNA levels in vivo, whereas IL-18 gene expression was slightly decreased. These data indicate that a persistent shift toward an IFN-gamma-dominated type 1 (Th1/cytotoxic T cell type 1) T-cell reaction pattern occurred within the thoracic lymph nodes of silicotic animals. Thus a mutual activation of lymphocytes and macrophages may maintain the chronic inflammatory changes that characterize silicosis.

Upregulation of matrix metalloproteinase-9 in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis.

It was investigated (1) whether metalloproteinase-9 (MMP-9), MMP-3, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, the natural tissue inhibitor of MMP-9) are increased in the CSF of patients with Lyme neuroborreliosis and (2) whether macrophages can express MMP-9 when stimulated with Borrelia burgdorferi. Zymography showed MMP-9 activity in 26 of 31 (84%) CSF samples from patients with acute stage 2 Lyme neuroborreliosis, but not in 20 controls with non-inflammatory neurological disorders. Activity of MMP-2 was detected in all CSF samples in both patients with neuroborreliosis and controls, suggesting a constitutive release of MMP-2. Using enzyme linked immunosorbent assay (ELISA) MMP-3 (which can activate MMP-9) was detected in low concentrations in the CSF of 13 of 29 patients with neuroborreliosis, but not in controls. TIMP-1 was increased twofold in CSF samples from patients with neuroborreliosis in comparison with the controls. MMP-9 activity was induced in vitro in a mouse macrophage cell line (RAW 264.7) when stimulated with two different genospecies of B burgdorferi (B garinii, B afzelii ). This MMP-9 activity was reduced in a dose dependent manner when macrophages stimulated with B burgdorferi were coincubated with NF-kappaB SN50, a cell permeable peptide which inhibits the translocation of NF-kappaB into the nucleus of stimulated cells. The data show that (1) MMP-9 activity is present in the CSF of patients with neuroborreliosis, (2) macrophages stimulated with B burgdorferi are a possible source of MMP-9 increase, and (3) activation of NF-kappaB may play a part in the upregulation of MMP-9 by B burgdorferi.

[The unequal clinical profile, quality of life and hospital mortality in patients undergoing aortocoronary bypass in the public and private centers of Catalonia. The CIRCORCA Study]. / Desigual perfil clínico, calidad de vida y mortalidad hospitalaria en pacientes operados de injerto aortocoronario en centros públicos y privados de Cataluña. El estudio CIRCORCA.

INTRODUCTION AND AIMS: The influence of the type of health care funding and management of hospital centres on hospital mortality in coronary artery bypass surgery (CABG) has not been analyzed in detail. We therefore assessed clinical and quality of life preoperative profiles and in-hospital mortality in public and private patients undergoing coronary bypass surgery in Catalonia. METHODS: Clinical questionnaires, Duke Activity Status Index (DASI) and SF-36 were preoperatively administered to all patients undergoing first coronary bypass surgery without associated procedures in Catalonia between November 1996-June 1997. In-hospital morbidity and mortality were recorded. RESULTS: Predictors of in-hospital death, including DASI, SF-36 and comorbidity scores, were significantly worse in public than in private patients. In-hospital mortality rate was more than ten times greater in public than in private patients (8.2% vs 0.7%; p < 0.001). Multivariate analysis identified private funding of health care, among others, as an independent predictor of in-hospital survival. Non evidence-based indications for surgery were significantly more common in private than in public patients (6% vs 0.7%, p < 0.001). CONCLUSIONS: a) In catalonia, the risk profile of public patients undergoing coronary bypass surgery was significantly higher than that of private patients, accounting, at least in part, for a remarkable mortality difference; b) non evidence-based indications for surgery were more common in private than in public patients; c) these unequal patterns raise questions about the adequacy of care and referral patterns in both private and public sectors.

Histopathological changes in enlarged thoracic lymph nodes during the development of silicosis in rats.

Silicosis is primarily a fibrotic lung disease which also affects the draining lymph nodes. In the present study, we examined the lymph nodes of rats from 2 weeks to 52 weeks after an 8-day silica aerosol exposure. Parallel to the typical silicotic changes in the lungs, profound alterations occurred in both posterior mediastinal lymph nodes. The weight of the lymph nodes progressively increased from 3.5-fold to 35-fold at 52 weeks after silica exposure. The weight increase was accompanied by an early increase of T cells and preferentially of CD4+ cells at 2 weeks, which converted into a B cell increase at 6 weeks. Histologically, a leukocyte influx without apparent structural changes was noted at 2 weeks whereas at 6 weeks, germinal centers and T cell regions were disappearing and macrophages accumulated in granuloma-like structures which were randomly scattered throughout the lymphoid tissue. Within the granulomas, macrophages were detected that carried ingested silica particles without apparent signs of degeneration or apoptosis. At 52 weeks after silica exposure, macrophage granulomas persisted without induction of fibrosis in both lymph nodes, and T and B cells were now evenly distributed within the tissue. These data extend our previous findings on lymphocyte and macrophage activation and indicate that the early and marked disorganization of draining lymph node structures may contribute to the immune abnormalities in silicosis.

Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis.

The oxidative metabolism of xenobiotics is effected mainly by cytochrome P450 enzymes (CYP), which are expressed as a family of genetically related enzymes primarily in hepatocytes. The pancreas is among the extrahepatic tissues expressing CYP, and it has been suggested that intermediates generated by them might be of pathogenetic significance for diseases of the pancreas such as chronic pancreatitis. We studied 10 surgical resection specimens by immunohistochemistry with polyclonal antibodies against recombinant human CYP 1A1, 1A2, 2C9, 2E1, and 3A and used tissues from 11 normal pancreata as controls. In addition, we assayed microsomal preparations for their capacity to metabolize verapamil. In normal pancreata weak to moderate expression of all enzymes was demonstrated immunohistochemically in up to 50% of duct epithelia, acinar cells, and islet cells. In contrast, in chronic pancreatitis an up-regulation was observed, with immunohistochemical positivity in some cases in up to 100% of duct epithelia and acinar cells. The oxidative capacity of microsomal preparations from chronic pancreatitis was higher than that of preparations obtained from control tissues; compared to liver microsomes, however, it was low. The up-regulation of CYP may have pathogenetic significance for chronic pancreatitis. Yet considering the pancreas' capacity for conjugation reactions, conceivably low levels of reactive intermediates could effectively undergo inactivation.