Advantages of laserphyrin compared with photofrin in photodynamic therapy for bile duct carcinoma

Background

The aim of this study was to compare the effects of laserphyrin-PDT (L-PDT) on biliary cancer with those of the conventional photosensitizer, photofrin-PDT (P-PDT).

Methods

An animal tumor model was established by inoculation of NOZ cells in 4-week-old male BALB/c mice. The laser light wavelength was set at 630 nm for P-PDT and 660 nm for L-PDT, at a frequency of 10 Hz. Each group received a total energy flux of 60 J/cm². The proportion of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling)-positive cells, expression of VEGF (vascular endothelial growth factor) and the PCNA (proliferating cell nuclear antigen)-labeling index (LI) were assessed after PDT.

Results

L-PDT had significantly more potent apoptotic effects at 48 and 72 h after light exposure compared with P-PDT (P < 0.001). The mean PCNA-LI was significantly lower in the L-PDT group than the P-PDT group and the index was significantly lower at several time points after PDT (6, 12, 24, 48 and 72 h after laser light exposure) in the L-PDT than P-PDT (P < 0.001 vs. control). The cell proliferative activity was significantly decreased at 12 and 24 h after P-PDT compared with the control (P < 0.001). VEGF expression was significantly higher at 3 h after L-PDT compared with the control (P < 0.05), whereas it was significantly higher at many time points after P-PDT (3, 6, 48 and 72 h; P < 0.05 vs. control).

Conclusions

L-PDT is a better approach for biliary cancer than the conventional P-PDT, based on its potent apoptotic and cytostatic effects.     

Retrograde coronary sinus cardioplegia cannula placement under short-time circulatory arrest in surgery for a ruptured type A dissection with a previous coronary artery bypass

A 79-year-old woman was referred to undergo surgery for a type A dissection. The patient had a history of previous coronary artery bypass. She was in shock and had a hematoma surrounding the ascending aorta and the heart. In this case, a coronary sinus cardioplegia cannula was placed under a short period of circulatory arrest via a small atriotomy, and the atriotomy was closed immediately to establish selective cerebral perfusion.     

Radical resection of a pleomorphic carcinoma after relieving airway obstruction by the endobronchial snare method

A 69-year-old man was hospitalized for fever and cough. He was diagnosed with and treated for an abscess in the left lower jaw and pneumonia by an otolaryngologist, but the pneumonia persisted with no improvement. Chest computed tomography revealed the presence of a heterogeneous torose lesion in the inlet of the left upper bronchus, and bronchoscopy revealed an endobronchial tumor with a smooth surface. An episode of sudden dyspnea occurred and was resolved after the patient changed his sitting position. We concluded that this symptom occurred because the tumor was incarcerated in the left lower lobe bronchus. The tumor was excised by bronchofi berscopic snare resection under tracheal intubation. It was found to be a pleomorphic carcinoma, and left upper lobectomy was performed. There has been no recurrence during the 3 years since the operation.     

The primary site of the acrocephalic feature in Apert Syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling

Activation of osteoblastic bone anabolism in the calvarial sutures is considered to be the essential pathologic condition underlying mutant FGFR2-related craniofacial dysostosis. However, early clinical investigations indicated that abnormal cartilage development in the cranial base was rather a primary site of abnormal feature in Apert Syndrome (AS). To examine the significance of cartilaginous growth of the cranial base in AS, we generated a transgenic mouse bearing AS-type mutant Fgfr2IIIc under the control of the Col2a1 promoter-enhancer (Fgfr2IIIc(P253R) mouse). Despite the lacking expression of Fgfr2IIIc(P253R) in osteoblasts, exclusive disruption of chondrocytic differentiation and growth reproduced AS-like acrocephaly accompanied by short anterior cranial base with fusion of the cranial base synchondroses, maxillary hypoplasia and synostosis of the calvarial sutures with no significant abnormalities in the trunk and extremities. Gene expression analyses demonstrated upregulation of p21, Ihh and Mmp-13 accompanied by modest increase in expression of Sox9 and Runx2, indicating acceleration of chondrocytic maturation and hypertrophy in the cranial base of the Fgfr2IIIc(P253R) mice. Furthermore, an acquired affinity and specificity of mutant FGFR2IIIc(P253R) receptor with FGF2 and FGF10 is suggested as a mechanism of activation of FGFR2 signaling selectively in the cranial base. In this report, we strongly suggest that the acrocephalic feature of AS is not alone a result of the coronal suture synostosis, but is a result of the primary disturbance in growth of the cranial base with precocious endochondral ossification.     

Sitagliptin added to treatment with ongoing pioglitazone for up to 52 weeks improves glycemic control in Japanese patients with type 2 diabetes

Aims/Introduction:  Patients with type 2 diabetes mellitus often require treatment with more than one oral antihyperglycemic agent to achieve their glycemic goal. The present study was carried out to assess the efficacy and safety of sitagliptin as add‐on therapy in Japanese patients with type 2 diabetes mellitus inadequately controlled (HbA1c ≥ 6.9% and <10.4%) on pioglitazone monotherapy (15–45 mg/day).Materials and Methods:  In the initial 12‐week, double‐blind treatment period, patients were randomized (1:1) to sitagliptin 50 mg/day (n = 66) or placebo (n = 68), followed by a 40‐week open‐label treatment period in which all patients received sitagliptin 50 mg/day that could have been increased to 100 mg/day for patients meeting predefined glycemic parameters.Results:  After 12 weeks, mean changes from baseline in HbA1c (the primary end‐point), fasting plasma glucose and 2‐h post‐meal glucose were −0.8%, −0.9 mmol/L and −2.7 mmol/L, respectively, in the sitagliptin group compared with placebo (all P < 0.001). The incidence of adverse experiences during the double‐blind treatment period was similar in both treatment groups, and the incidences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, improvements in glycemic parameters with sitagliptin treatment were maintained and sitagliptin was generally well tolerated.Conclusions:  Sitagliptin as add‐on therapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus inadequately controlled on pioglitazone monotherapy. This trial was registered with ClinicalTrials.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00372060","term_id":"NCT00372060"}}NCT00372060). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00120.x, 2011)     

GABA(A) receptor-mediated presynaptic inhibition on glutamatergic transmission

We investigated the functional roles of presynaptic GABA_A receptors on excitatory nerve terminals in contributing to spontaneous and action potential-evoked glutamatergic transmission to rat hippocampal CA3 pyramidal neurons. Single CA3 neurons were mechanically isolated with adherent nerve terminals, namely the ‘synaptic bouton preparation’, and spontaneous glutamatergic excitatory synaptic potentials (sEPSCs) and EPSCs evoked by focal electrical stimuli of a single presynaptic glutamatergic boutons (eEPSCs) were recorded using conventional whole-cell patch recordings. Selective activation of presynaptic GABA_A receptors on these excitatory nerve terminals by muscimol, markedly facilitated sEPSCs frequency but inhibited eEPSC amplitude. The facilitation of sEPSC frequency was completely occluded by GABA_A receptor-Cl⁻ channel blockers bicuculline or penicillin (PN). PN itself concentration-dependently inhibited the GABA_A receptor response induced by bath application of muscimol, but had no effect on the glutamate receptor response. In addition, pretreatment with a blocker of the Na⁺, K⁺, 2Cl⁻ co-transporter type 1 (NKCC-1), bumetanide, prevented the muscimol-induced inhibition of eEPSCs. The results indicate that activation of presynaptic GABA_A receptors directly depolarizes glutamatergic excitatory nerve terminals and thereby differentially modulates sEPSCs and eEPSCs.     

Large-scale heterogeneous representation of sound attributes in rat primary auditory cortex: from unit activity to population dynamics

Recent evidence indicates the existence of pyramidal cells (PCs) and interneurons with nontrivial tuning characteristics for sound attributes in the primary auditory cortex (A1) of mammals. These neurons are functionally distributed into layers and sparsely organized at a small scale. However, their topological locations at a large scale in A1 have not yet been investigated. Furthermore, these neurons are usually classified from fine maps of attribute-dependent spiking activity, and not much attention is paid to population postsynaptic potentials related to their activity. We used extracellular recordings obtained from multiple sites in A1 of adult rats to determine neuronal codifiers for sound attributes defined by coarse representations of the population dose-response curves. We demonstrated that these codifiers, majorly involving PCs, are heterogeneously distributed along A1. Spiking activity in these neurons during stimulation was correlated to β (12-25 Hz) and low γ (25-70 Hz) postsynaptic oscillations in the infragranular layer, whereas in the supragranular layer, better correlations were found with high γ (70-170 Hz) oscillations. The time-frequency analysis of the postsynaptic potentials showed a transient broadband power increase in all layers after the stimulus onset that was followed by a sustained high γ oscillation in the supragranular layer, fluctuations in the laminar content of the low-frequency oscillations, and a global attenuation in the low-frequency powers after the stimulus offset that happened together with a long-lasting strengthening of the β oscillations. We concluded that, for rats, sounds are codified in A1 by segregated networks of specialized PCs whose postsynaptic activity impinges on the emergence of sparse/dense spiking patterns.