Age-dependent carcinogenic susceptibility in rat liver is related to potential of gap junctional intercellular communication

Connexin 32 (Cx32) is a major gap junction protein in the liver. The authors previously demonstrated that transgenic rats carrying a dominant negative mutant of Cx32 (Cx32ΔTg) have much decreased capacity for gap junctional intercellular communication (GJIC) and increased susceptibility to diethylnitrosamine (DEN)-induced hepatocarcinogenesis as compared to littermate wild-type (wt) rats. To evaluate the age-dependent susceptibility to DEN-induced hepatocarcinogenesis and alteration of GJIC function, male Cx32ΔTg and wt rats at 10, 30, or 85 weeks old were given a single intraperitoneal administration of DEN (40 mg/rat) and sacrificed 12 weeks later. The number and area of glutathione S-transferase placental form (GST-P)-positive preneoplastic foci were significantly increased in the liver of 10- and 30-wk-old Cx32ΔTg rats compared with age-matched wt. However, in the 85-wk-old rats, both Cx32ΔTg and wt rats had similarly large number and area of GST-P-positive foci, and the difference was not significant. Interestingly, function of hepatic GJIC was reduced and protein and mRNA expression of Cx32 were decreased with aging in wt rats. These results suggest that a decline of hepatic intercellular communication through gap junction results in increased susceptibility to DEN-induced hepatocarcinogenesis in aged rats.     

Comparative trial of two intravenous doses of granisetron (1 versus 3?mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial

Purpose  

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy.     

Acetaminophen administration in a patient with Gilbert's syndrome

The patient was an 8‐year‐old Japanese girl with Gilbert's syndrome (GS). Based on the DNA analysis, she was homozygous for a T‐to‐G transversion at nucleotide position 1456 in the UGT1A1 gene, leading to the substitution of aspartate for tyrosine at position 486 of the UGT1A1 enzyme. Because this mutation is located in an exon common to UGT1A genes, all the UGT1A enzymes may be affected. It is well‐known that UGT1A1, UGT1A6 and UGT1A9 enzymes glucuronidate acetaminophen. To evaluate acetaminophen tolerance in the patient, serum acetaminophen levels were determined after oral administration of acetaminophen (15 mg/kg). The maximum serum acetaminophen level reached (12.8 µg/mL) was far below the toxic level. The finding suggested that the usual therapeutic dose of acetaminophen is safe for the GS patient. The combination of mutation analysis in UGT1A1 and acetaminophen loading test may be useful to avoid adverse effect in GS patients.     

The first case of 4-hydroxybutyric aciduria in Japan

We report a boy with 4-hydroxybutyric aciduria resulting from a deficiency of succinic semialdehyde dehydrogenase (SSADH). A boy, 1 year 5 months, showed delayed walk with hypotonia and could not speak meaningful words. The blood levels of lactate, pyruvate and amino acids were not elevated. Head magnetic resonance imaging (MRI) and electroenchephalography (EEG) were normal. Urinary organic acid analysis with gas chromatography-mass spectrometry (GCMS) revealed increased levels of 4-hydroxybutyric acid, glutaric acid, adipic acid and suberic acid. The concentrations of 4-hydroxybutyric acid and gamma-aminobutyric acid (GABA) were elevated in the serum and cerebrospinal fluid (CSF). SSADH activity in cultured lymphoblasts was 4.5% of the normal level. So far as we know this is the first Japanese patient diagnosed as 4-hydroxybutyric acid. Urinary organic acid analysis is necessary for the diagnosis of patients with unexplained psychomotor retardation.     

Evaluation of sensory function after median nerve decompression in carpal tunnel syndrome using the current perception threshold test

The recovery level for sensory function after carpal tunnel release for the treatment of idiopathic carpal tunnel syndrome (CTS) was assessed with the current perception threshold (CPT) test. Seventeen CTS patients (21 hands) were followed, and the CPTs at the index finger of each patient was measured preoperatively and at 1, 3, and 6 months postoperatively. After carpal tunnel release, there was significant recovery of CPT at all stimulation frequencies, indicating improvement of all sensory functions including sensations of temperature, pain, touch, and vibration.     

Hepatocyte growth factor,a biomarker of macroangiopathy in diabetes mellitus

Atherosclerotic involvements are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis(CA) being a common risk-factor for prospective crisis of coronary artery diseases(CAD) and/or cerebral infarction(CI) in DM subjects. From another point of view, several reports have supplied augmenting proof that hepatocyte growth factor(HGF) has a physiopathological part in DM involvements. HGF has been a mesenchymal-derived polyphenic factor which modulates development, motion, and morphosis of diverse cells, and has been regarded as a humor intermediator of epithelial-mesenchymal interplays. The serum concentrations of HGF have been elevated in subjects with CAD and CI, especially during the acute phase of both disturbances. In our study with 89 type 2 DM patients, the association between serum concentrationsof HGF and risk-factors for macrovascular complicationsinclusive of CA were examined. The average of serumHGF levels in the subjects was more elevated than thereference interval. The serum HGF concentrations associated positively with both intimal-media thickness(IMT)(r = 0.24, P = 0.0248) and plaque score(r = 0.27, P =0.0126), indicating a relationship between the elevatedHGF concentrations and advancement of CA involvements. Multivariate statistical analysis accentuated thatserum concentrations of HGF would be associated inde-pendently with IMT(standardized = 0.28, P = 0.0499).The review indicates what is presently known regardingserum HGF might be a new and meaningful biomarkerof macroangiopathy in DM subjects.     

Endoscopic submucosal dissection for colorectal neoplasms: A review

The introduction of colorectal endoscopic submucosal dissection(ESD)has expanded the application of endoscopic treatment,which can be used for lesions with a low metastatic potential regardless of their size.ESD has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal resection.Moreover,in the past,surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum,regardless of the depth of invasion,as endoscopic resection of these lesions was technically difficult.Therefore,a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal lesions.On the other hand,ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty,longer procedural duration,and increased risk of perforation.To diversify the available endoscopic treatment strategies for superficial colorectal neoplasms,endoscopists performing ESD need torecognize its indications,the technical issues involved in its application,and the associated complications.This review outlines the methods and type of devices used for colorectal ESD,and the training required by endoscopists to perform this procedure.     

Pulmonary arterial infusion therapy for lung metastasis of colorectal cancer

We have developed a pulmonary arterial infusion therapy for lung metastasis of colorectal cancer. Catheterization into pulmonary artery followed by occlusion with ballooning enabled the stasis of blood flow in the unilateral lung for 30 minutes. CDDP was infused via catheter to occluded pulmonary artery. Although no serious adverse events occurred in 5 cases, a tumor reduction in size was not observed. Loco-regional therapy for lung metastasis of colorectal cancer is limited because of recent progress of systemic therapy. However, a development of the procedure of pulmonary arterial infusion may enable a future success of local therapy for lung metastasis of colorectal cancer with a new drug, which is effective in such a short time disposure to tumor as 30 minutes.