Reversibility of the adverse effects of 1-bromopropane exposure in rats.

Previous experiments indicated that 1-bromopropane (1-BP), an alternative to chloroflurocarbons, is neurotoxic and inhibits spermiation in the testis. Here we investigated the reversibility of the toxic effects of 1-BP in rats. Male Wistar rats were divided into three equal groups of 24 each and exposed by inhalation to 0, 400 or 1000 ppm of 1-BP for 6 weeks (8 hrs/day, 7 days/week). Eight rats from each group were sacrificed at the end of 6 weeks exposure, and at 4 and 14 weeks after the end of exposure, to assess the recovery processes. We studied sperm count, motility, morphology and testicular histopathology, as well as blood pressure, skin temperature and hindlimb muscle strength. At the end of 6 weeks of exposure to 1000 ppm (0 week recovery), testicular weight, epididymal weight, sperm count and motility were low, morphologically abnormal sperm were increased and spermatogenic cells showed diffuse degeneration. These changes did not show full recovery at 14 weeks recovery, with the exception of the prostate and seminal vesicular weights, which recovered back to control values. At 400 ppm, increased retained spermatids at 0 week recovery returned to normal at 4 weeks recovery. Exposure to 1000 ppm produced sustained reduction of hindlimb muscle strength at 14 weeks recovery, whereas normalization of the skin temperature and blood pressure was noted after transient changes. Our study showed that the effect of 1-BP on spermatogenesis is dose-dependent; low exposure inhibited spermiation and hormone-dependent organ weight reduction and these changes were transient, while a higher dose of 1000 ppm 1-BP caused persistent depletion of spermatogenic cells.     

Orally-administered caspase inhibitor PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against alpha-fas-induced liver injury in a mouse model

In a mouse model of alpha-Fas-induced acute liver injury, the orally-administered caspase inhibitor PF-03491390 (formerly named IDN-6556) was retained in the liver for prolonged periods with a low systemic exposure. Reductions in the elevated plasma levels of alanine aminotransferase (ALT) revealed that the retention of PF-03491390 in the liver exerted a hepatoprotective effect, even when pre-administered to mice 4 h before alpha-Fas insult. Prolonged retention of PF-03491390 in the liver after oral administration has the benefit of low systemic exposure, making this a beneficial agent for the treatment of liver diseases.     

Experimental AA amyloidosis in mice is inhibited by treatment with triptolide, a purified traditional Chinese medicine

The effect of triptolide, which is isolated from Tripterygium Wilfordii, on induction and development of murine AA amyloidosis was studied. In the first experiment, we examined the ability of triptolide to inhibit initiation of amyloidosis. Oral or intraperitoneal administration of 480 microg/kg/day triptolide inhibited splenic amyloid deposition in both rapid and chronic induction models of mouse AA amyloidosis. Moreover, serum amyloid A (SAA) and interleukin (IL)-6 levels were also suppressed remarkably. Triptolide also immediately decreased SAA levels and reduced the incidence of amyloidosis even under conditions of high SAA levels. In the second experiment, we evaluated the influence of triptolide on development and resorption of amyloid deposition. Amyloid deposition was induced in mice by 28 daily injections of casein. After splenic and hepatic biopsies to confirm the presence of amyloid deposits, the mice immediately started to receive daily injections of 480 microg/kg/day triptolide with or without casein. Treatment with triptolide for 35 days and 105 days prevented deposition of amyloid and promoted resorption of splenic amyloid deposits. In conclusion, we show for the first time that triptolide inhibits induction and development of experimental murine amyloidosis. These results suggest that through suppression of IL-6, triptolide can reduce production of SAA. Amyloid deposition is prevented when levels of the amyloid-forming precursor protein SAA are decreased significantly.     

A case of subdural hematoma associated with dural metastasis of lung cancer

A 62-year-old male developed headache, restlessness and left hemiparesis three months after being diagnosed with advanced lung cancer. Computed tomography on admission revealed a crescent-shaped, mixed intensity area in the right fronto-parietal subdural region and multiple tumors in the brain parenchyma. Under a diagnosis of chronic subdural hematoma and multiple brain metastases due to lung carcinoma, burr hole irrigation was performed. Adenocarcinoma cells were found in the dura matter and hematoma. Nontraumatic chronic subdural hematoma secondary to dural metastasis is a very rare condition. Only 52 cases of such spontaneous subdural hematoma have been reported. We describe the clinical features and discuss the mechanism referring to the pertinent literature.     

Lung large cell carcinoma producing granulocyte-colony-stimulating factor

In recent years, tumors producing granulocyte-colony-stimulating factor have been reported in an increasing number of patients, the majority of which have lung cancer. We experience a case of lung carcinoma producing granulocyte-colony-stimulating factor treated by resection and chemotherapy. He remains well 2 years and 10 months after surgery, with no recurrence of the carcinoma.     

Multiple necrotic nodules of the liver simulating liver metastasis

A 70-year-old man was referred to our hospital due to anemia and elevated serum tumor marker levels. He had advanced colon cancer, and hepatic lesions were found incidentally. On ultrasonography (US) and computed tomography (CT), the hepatic lesions had a maximum diameter of 20 mm and were located in Couinaud's segments V, VI, VII, and VIII, which suggested liver metastasis. On early- and late-phase CT during hepatic arteriography (CTHA), all of the lesions had rim enhancement. On early-phase CT during arterioportography (CTAP), all of the lesions were seen as nodules with an irregular perfusion defect, and on late-phase CTAP, all the lesions gradually became iso-dense, and their shape and size changed. Based on the CTAP findings, these lesions were thought to be fibrotic tumors. Partial resection of the liver (including the lesions in Couinaud's segments V and VIII) was done. Histological examination revealed that the lesions were necrotic nodules. Thus, CT angiography (CTHA and CTAP) was useful for identifying necrotic nodules, because their appearance on this modality is different from that of liver metastases.     

Chemotherapy-induced sclerosing cholangitis as a rare indication for resection: Report of a case

Bile duct stricture due to chemotherapy-induced sclerosing cholangitis (CISC) is a potentially fatal complication of hepatic arterial infusion chemotherapy (HAIC). It is managed primarily with medical treatment and biliary stenting. We report a rare case of a CISC-related biliary stricture requiring resection. The patient had been receiving adjuvant HAIC for 11 months after a curative liver resection for hepatocellular carcinoma, when clinically overt cholangitis developed. Radiologic and biopsy findings suggested a CISC-related biliary stricture limited to the common hepatic duct. We discontinued HAIC and started corticosteroid treatment, which finally became ineffective. Endoscopic biliary stenting was impossible because of her severe biliary sclerosis, necessitating resection of the stricture, which was confirmed histologically to be secondary sclerosing cholangitis. The patient has shown no signs of recurrent cholangitis for 12 postoperative months since her operation. Thus, resection could be a treatment option for a CISC-related biliary stricture in selected patients.     

Comparison of acellular pertussis-based combination vaccines by Japanese control tests for toxicities and laboratory models for local reaction

Two batches each of diphtheria–tetanus–acellular pertussis vaccine (DTaP) and that combined with inactivated polio vaccine purchased from the U.S.A., European and Asian markets were compared with Japanese DTaPs by Japanese control tests for DTaP and laboratory models for local reaction. All the imported vaccines met Japanese criteria for toxicities of acellular pertussis vaccine except for the toxicity to mouse weight gain (body weight decreasing (BWD) toxicity). When injecting into mouse footpad, rabbit back skin and mouse quadriceps muscle, the imported vaccines induced much severer inflammation and tissue injury comparing to Japanese DTaPs irrespective of animal species, injection site and injection volume suggesting that these vaccines may induce stronger local reactogenicity.     

Immunohistochemical study of immunoglobulin light chain amyloidosis with antibodies to the immunoglobulin light chain variable region

To detect immunoglobulin (Ig) light chain amyloidosis (AL amyloidosis) in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry, polyclonal antibodies were generated against synthetic peptides corresponding to amino acids 1-19 of the Ig lambda light chain V lambda VI subgroup (anti-V lambda VI (1-19)) and the Ig kappa light chain Vkappa I subgroup (anti-Vkappa I (1-19)). Anti-V lambda VI (1-19) antibody reacted with amyloid deposits in 21 of 22 Alambda amyloidosis cases, and anti-Vkappa I (1-19) antibody reacted with amyloid deposits in 10 of 11 Akappa amyloidosis cases. Immunoreactivity varied in intensity by case and within specimens. Surprisingly, amyloid deposits were positive for anti-V kappa I (1-19) staining in one case of Alambda amyloidosis. Analysis of anti-V lambda VI (1-19) and anti-Vkappa I (1-19) antibody reactivity by ELISA showed some cross-reactivity with peptides other than antigen peptides. The antibodies were not reactive in all cases of AL amyloidosis examined but may be useful, together with anti-Ig constant region antibodies, for immunohistochemical diagnosis of AL amyloidosis.     

N-Methyl-D-Aspartate (NMDA) and non-NMDA receptor antagonists suppress the superior sagittal sinus-evoked activity of C1 spinal neurons responding to tooth pulp electrical stimulation in rats

The aim of the present study was to determine whether there is a convergence of inputs from tooth pulp (TP) and the superior sagittal sinus (SSS) on rat C1 spinal neurons, and to examine the effects of iontophoretically applied N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists on the SSS-evoked activity of C1 neurons. Extracellular single unit-recordings were made from 20 C1 units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram signal, using a multibarrel electrode in pentobarbital-anesthetized rats. Ninety percent of C1 neurons (18/20) responding to TP stimulation also responded to the SSS stimulation. These neurons were considered to be SSS-afferent inputs from Aδ-fibers (5.8 ± 0.6 m/s; n = 18), based on the calculation of nerve conduction velocity. After the iontophoretic application (30, 50, and 70 nA) of an NMDA receptor blocker (5R-10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cycloheptene-5,10-imine hydrogen maleate (MK801) or a non-NMDA receptor blocker (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX), the mean number of spikes responding to the SSS stimulation significantly decreased (30, 50, and 70 nA; P < 0.05). These results suggest that there is a convergence of inputs from SSS and TP afferents on C1 neurons; it is possible that both NMDA and non-NMDA receptors located on C1 neurons may be targets for the treatment of the trigeminal referred pain associated with migraine.