Prospective randomised comparison of organ-preserving pancreatic head resection with pylorus-preserving pancreaticoduodenectomy

Background and aims In a prospective, randomised, control trial organ-preserving pancreatic head resection (OPPHR) was compared with pylorus-preserving pancreaticoduodenectomy (PPPD) to assess the advantages and disadvantages of each type of operation.Patients and methods Forty patients were allocated randomly to either the OPPHR (n=20) or the PPPD (n=20) group. The surgical data, postoperative complications, induction of diabetes mellitus, postoperative pain and quality of life 1 year, postoperatively, were considered.Results The two study groups of 20 patients were well balanced with regard to sex, age, chronic pancreatitis history and indication for surgery. The duration of the operation for OPPHR and PPPD was 142.5±4.9 and 278±6.9 min, respectively (P<0.05). The postoperative mortality in each group was zero. After OPPHR and PPPD, the morbidity was 0 and 40%, respectively (P<0.05). The duration of hospital stay was also significantly different: 8.05±0.9 vs 13.8±3.9 days (P<0.05). After 1 year the pain relief was effective in both groups, but three patients acquired diabetes mellitus after PPPD; the body weight had increased by 7.8±0.9 and 3.2±0.3 kg after OPPHR and PPPD, respectively (P<0.05).Conclusion The two procedures are equally safe and effective with regard to pain relief, but OPPHR is superior to PPPD not only in the operation data and morbidity, but also in the quality of life 1 year postoperatively. OPPHR should be regarded as a recommended procedure in the treatment of chronic pancreatitis.Presented at the 6th Congress of the European Hepato–Pancreato–Biliary Association, 25–28 May 2005, Heidelberg, Germany and published in abstract form as HPB (2005) 7(Suppl. No. 1):73.     

The decrease of dopamine D₂/D₃ receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB₁ cannabinoid receptors in Parkinson's disease: a preliminary autoradiographic study with the selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015

Cannabinoid type-1 receptors (CB?Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB?Rs play an important role in the regulation of motor activities in the striatum. In the present study, we used human brain samples to examine the relationship between CB?R and dopamine receptor density in case of Parkinson's disease (PD). Post mortem putamen, nucleus caudatus and medial frontal gyrus samples obtained from PD patients were used for CB?R and dopamine D?/D? receptor autoradiography. [12?I]SD7015, a novel selective CB?R inverse agonist, developed by a number of the present co-authors, and [3H]raclopride, a dopamine D?/D? antagonist, were used as radioligands. Our results demonstrate unchanged CB?R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (L-DOPA). At the same time dopamine D?/D? receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 ± 10.00 fmol/g, PD: 3.73 ± 0.07 fmol/g (mean ± SEM), p<0.05) and nucleus caudatus (control: 30.26 ± 2.48 fmol/g, PD: 12.84 ± 5.49 fmol/g, p<0.0005) samples. In contrast to the putamen and the nucleus caudatus, in the medial frontal gyrus neither receptor densities were affected. Our data suggest the presence of an unaltered CB?R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB?R population which, in line with the conclusion of earlier publications, may be utilized as a pharmacological target in the treatment of PD. Furthermore we found discrepancy between a maintained CB?R population and a decreased dopamine D?/D? receptor population in PD striatum. The precise explanation of this conundrum requires further studies with simultaneous examination of the central cannabinoid and dopaminergic systems in PD using higher sample size.     

Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot

Activated clotting factors are down-regulated by two major mechanisms which involve protease inhibitors or proteolytic degradation. To date, no down-regulating mechanism for activated factor XIII (FXIIIa) has been demonstrated. As the hemostatic plug contains polymorphonuclear granulocytes (PMNs) rich in proteolytic enzymes, we tested if these proteases are released in fibrin clots, and become involved in the down-regulation of FXIIIa. The supernatant of stimulated granulocytes proteolytically degraded and inactivated FXIIIa. In the fibrin clot formed from fibrinogen solution elastase, cathepsin G and matrix metalloprotease-9 (MMP-9) were released from granulocytes without any external stimulus. PMN proteases released in fibrin clot exerted a fibrinolytic effect and almost completely degraded both FXIII subunits. The elastase inhibitor, ONO 5046, partially inhibited the proteolytic degradation of FXIII in PMN-supplemented fibrin clots. Cathepsin G and MMP-9 inhibitors provided less protection; in these cases intermediate split products accumulated. The proteolytic degradation of FXIII by PMNs was also significant when the clot was made from whole plasma. The main plasma protease inhibitor, alpha1-antitrypsin, provided only partial protection. In the fibrin clot which contained alpha1-antitrypsin FXIIIa was degraded by PMN proteases significantly faster than cross-linked fibrin. The results suggest that the degradation of FXIII subunits by the concerted action of PMN proteases released within the clot represents a novel mechanism for the down-regulation of FXIIIa.     

Non-fibrillar beta-amyloid abates spike-timing-dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors

Cognitive decline in Alzheimer's disease (AD) stems from the progressive dysfunction of synaptic connections within cortical neuronal microcircuits. Recently, soluble amyloid beta protein oligomers (Abeta(ol)s) have been identified as critical triggers for early synaptic disorganization. However, it remains unknown whether a deficit of Hebbian-related synaptic plasticity occurs during the early phase of AD. Therefore, we studied whether age-dependent Abeta accumulation affects the induction of spike-timing-dependent synaptic potentiation at excitatory synapses on neocortical layer 2/3 (L2/3) pyramidal cells in the APPswe/PS1dE9 transgenic mouse model of AD. Synaptic potentiation at excitatory synapses onto L2/3 pyramidal cells was significantly reduced at the onset of Abeta pathology and was virtually absent in mice with advanced Abeta burden. A decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/N-methyl-D-aspartate (NMDA) receptor-mediated current ratio implicated postsynaptic mechanisms underlying Abeta synaptotoxicity. The integral role of Abeta(ol)s in these processes was verified by showing that pretreatment of cortical slices with Abeta((25-35)ol)s disrupted spike-timing-dependent synaptic potentiation at unitary connections between L2/3 pyramidal cells, and reduced the amplitude of miniature excitatory postsynaptic currents therein. A robust decrement of AMPA, but not NMDA, receptor-mediated currents in nucleated patches from L2/3 pyramidal cells confirmed that Abeta(ol)s perturb basal glutamatergic synaptic transmission by affecting postsynaptic AMPA receptors. Inhibition of AMPA receptor desensitization by cyclothiazide significantly increased the amplitude of excitatory postsynaptic potentials evoked by afferent stimulation, and rescued synaptic plasticity even in mice with pronounced Abeta pathology. We propose that soluble Abeta(ol)s trigger the diminution of synaptic plasticity in neocortical pyramidal cell networks during early stages of AD pathogenesis by preferentially targeting postsynaptic AMPA receptors.     

Micro-island damage with a nonablative 1540-nm Er:Glass fractional laser device in human skin

Background and objectives  Fractional photothermolysis produces micro-islands of thermal injury to the skin while preserving areas among treated tissue sites in order to promote wound healing. Histological changes associated with single and multiple passes of the 1540-nm Er:Glass fractional laser were examined using in vivo human skin.
Methods and materials  Panni of five abdominoplasty patients were treated intraoperatively with a Fractional Lux1540 erbium glass laser system at various laser parameters, with single and multiple passes. Biopsies were removed and examined using standard histological stains.
Results  Deep coagulated columns of collagen separated by regions of unaffected tissue were observed at variable fluence parameters. A direct correlation between the depth of penetration of the coagulated microcolumns and increasing energies was observed. Micro-islands of coagulation were ∼250 μm in diameter and separated by ∼800 μm of unaffected tissue. With multiple passes, significantly more disruption of the dermal–epidermal junction (DEJ) occurred at higher fluences. In contrast to the controlled fractional columns observed with single-pass treatments, nonuniform coagulated columns were distributed randomly throughout the tissue when instituting multiple passes over the same treatment region.
Conclusion  Micro-islands of thermal damage were observed at variable energy parameters. Pathological changes within the skin were clearly dependent on amount of energy and number of passes of the laser treatment. Significantly more superficial damage, accompanied by disruption of the DEJ was observed with multiple passes when compared with single pass at similar fluences. However, with multiple passes, depth of thermal injury did not increase with increasing energies but did disrupt the micro-island array observed with single-pass fractional treatments.     

Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d=45 to 53 μm) produced multifocal ischemia in anesthetized rats (n=7). Synchronous image sequences captured through a cranial window above the frontoparietal cortex revealed: Changes in membrane potential (voltage-sensitive (VS) dye method); cerebral blood flow (CBF; laser speckle contrast (LSC) imaging); and hemoglobin (Hb) deoxygenation (red intrinsic optical signal (IOS) at 620 to 640 nm). A total of 31 SD events were identified. The foci of five SDs were seen in the cranial window, originating where CBF was the lowest (56.9±9%), but without evident signs of infarcts. The hyperemic CBF responses to propagating SDs were coupled with three types of Hb saturation kinetics. More accentuated Hb desaturation was related to a larger decrease in CBF shortly after ischemia induction. Microsphere-induced embolization triggers SDs in the rat brain, relevant for small embolic infarcts in patients. The SD occurrence during the early phase of ischemia is not tightly associated with immediate infarct evolution. Various kinetics of Hb saturation may determine the metabolic consequences of individual SDs.     

Changes in the Expression of Pituitary Adenylate Cyclase-Activating Polypeptide in the Human Placenta during Pregnancy and Its Effects on the Survival of JAR Choriocarcinoma Cells

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with survival-promoting actions, has been observed in endocrine organs and is thought to play a role in reproductive functions, including pregnancy. PACAP occurs in two forms, 27 and 38 amino acid residues, with PACAP38 being the predominant form in human tissues. In the present study, we determined the concentrations of PACAP38 and PACAP27 in first-trimester and full-term human placentas using radioimmunoassay. We found high levels of PACAP38 and lower levels of PACAP27 in different parts of the full-term human placenta. PACAP38 content increased in the placenta during pregnancy, both on the maternal side and on the fetal side. The effects of PACAP on the survival of JAR human choriocarcinoma cells were investigated using flow cytometry and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell viability assay in cells exposed to the widely used chemotherapeutic agent methotrexate (MTX). It was found that PACAP neither influenced the survival of JAR cytotrophoblast cells nor affected cellular response to the death-inducing effect of the chemotherapeutic agent MTX. The present observations further support the significance of PACAP in the human placenta. The observation that PACAP did not influence the effects of MTX may have future clinical importance, showing that PACAP does not decrease the effects of certain chemotherapeutic agents.     

Placental proteins 12 and 14 in pre-eclampsia

The concentrations of circulating placental protein 12 (PP12) and placental protein 14 (PP14) were measured in 41 patients with pre-eclampsia and in 17 control subjects. The levels of PP12 were significantly elevated in patients with severe preeclampsia, whereas PP14 levels were unaffected. There was a negative correlation between the levels of both PP12 and PP14 and birthweight. PP12 and PP14 appear therefore to have different control mechanisms and, possibly, different cellular origins within the decidua.