Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster‐associated pain including post‐herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2–3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3–4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.     

Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.     

Changes in arrhythmogenic properties and five‐year prognosis after carbon‐ion radiotherapy in patients with mediastinum cancer

Introduction

Carbon‐ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon‐ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra‐cardiac cancer treated with carbon‐ion radiotherapy that included irradiating the heart.

Methods and Results

In April–December 2009, eight patients were prospectively enrolled (including two male, aged 72.5 ± 13.0 years). They were treated with 44–72 Gray equivalent (GyE), with their hearts exposed to 1.3–19.1 GyE. High‐resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre‐existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five‐year follow‐up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events.

Conclusion

Although this preliminary study has several limitations, carbon‐ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

     

Monocarboxylate transporter mediates uptake of lovastatin acid in rat cultured mesangial cells

To clarify the uptake mechanism(s) for statins, we examined whether monocarboxylate transporter (MCT) contributed to the uptake of lovastatin acid by rat cultured mesangial cells. Expression of mRNAs for MCT1, 2, and 4 was confirmed in mesangial cells. The uptake of lovastatin acid by mesangial cells increased with decreasing extracellular pH. There was clear overshooting in lovastatin acid uptake by the ATP-depleted cells in the presence, but not in the absence, of an inwardly directed H(+)-gradient. The representative MCT substrates/inhibitors inhibited the lovastatin acid uptake. In particular, the inhibition of lovastatin acid uptake by L-lactic acid at the concentration of 80 mM reached 70%, and L-lactic acid and valproic acid inhibited the uptake competitively. On preloading of mesangial cells with L-lactic acid or valproic acid, the lovastatin acid uptake was significantly stimulated. The inhibition constant of L-lactic acid for the lovastatin acid uptake was 32 mM, and this value is comparable to the Michaelis constant (>20 mM) of L-lactic acid for MCT4 described elsewhere. These results demonstrate that lovastatin acid was largely taken up by mesangial cells via MCT, and suggest that MCT4 might contribute to lovastatin acid uptake in the cells.     

Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects

In the present study, we examined whether polymorphisms in the ATP-binding cassette (ABC) transporter genes, MDR1, MRP1 and MRP2, were associated with their respective mRNA expression levels in duodenal enterocytes of 13 healthy Japanese volunteers. MDR1 genotypes of T-129C, G2677(A,T) and C3435T, MRP1 genotypes of G128C, C218T, G2168A and G3173A, and MRP2 genotypes of C-24T, G1249A, C2302T, C2366T and G4348A were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or direct sequencing. Mutations T-129C, G2677(A,T) and C3435T of MDRI gene were found at allele frequencies of 2/26, 16/26 and 12/26, respectively. Mutations G2168A of the MRPI gene and C-24T of the MRP2 gene were also found at allele frequencies of 1/26 and 6/26, respectively, whereas other mutations were not detected in MRP1 and MRP2 genes. The relative concentrations (mean +/- S.E.) of MDR1 mRNA to villin mRNA were 0.38 +/- 0.15, 0.56 +/- 0.14 and 1.13 +/- 0.42 in the subjects with C/C3435, C/T(3435) and T/T(3435), respectively, which supported the lower serum concentrations of digoxin after single oral administration in the subjects with the mutant T-allele at position 3435. Genetic collaboration between positions 3435 and 2677 was suggested, and those in G/G2677, G/(A,T)(2677) and T/(A,T)(2677) were 0.16 +/- 0.05, 1.10 +/- 0.40, and 0.63 +/- 0.16, respectively (p = 0.107). However, there was no remarkable effect of the G2168A of the MRP1 gene or of C-24T of the MRP2 gene on the relative MRP1 or MRP2 mRNA concentrations, respectively.     

Relationships between the in vitro cytotoxicity and transport characteristics of pirarubicin and doxorubicin in M5076 ovarian sarcoma cells, and comparison with those in Ehrlich ascites carcinoma cells

PURPOSE: We sought to determine whether the de novo resistance of M5076 ovarian sarcoma cells, which show sensitivity to pirarubicin (THP), to doxorubicin (DOX) is due to differences in the transport characteristics between THP and DOX, and the results were compared with those for drug-sensitive Ehrlich ascites carcinoma cells. METHODS: The in vitro cytotoxicity of the drugs was assessed by means of the tetrazolium dye assay. Transport experiments were performed by the rapid centrifugation method. RESULTS: In an in vitro cytotoxicity experiment, M5076 cells showed lower sensitivity to DOX than to THP, and the cytotoxicity of THP and DOX toward M5076 cells was lower than toward Ehrlich cells, and these results were similar to those of an in vivo experiment. This was due to the much lower expression of topoisomerase II in M5076 cells than in Ehrlich cells. The amount of intracellular DOX was found to be significantly lower than that of THP in both cell types, and furthermore, little free intracellular DOX was observed in M5076 cells, indicating that the low sensitivity of M5076 cells to DOX was partially a result of the low amount of intracellular DOX. There was no difference in the efflux rate, but there was an apparent difference in the uptake efficiency of the carrier between THP and DOX. CONCLUSIONS: These findings suggest that the cytotoxicities of THP and DOX toward M5076 and Ehrlich cells depend, at least in part, on the uptake efficiency of the carrier.     

The usefulness of MRI around the tentorial incisura for determining the mechanism of brain stem injury: a case report

We report a case of isolated brain stem injury caused by the tentorium cerebelli. A 17-year-old male was admitted to our hospital. Thirty minutes before admission, he was struck by another motorcycle while driving his own motorcycle. The Glasgow Coma Scale (GCS) was 10. He had no extremity weakness and his pupils were normal. CT scan showed no evidence of intracranial lesions except for facial bone fractures. His consciousness level improved to GCS 13 at 6 hours after admission. Follow-up CT scan was normal, however MRI 3 days after admission showed a contusion at the left lateral midbrain. He was discharged without any neurological deficits on 6 days after admission. Analysis of the distance between the brain stem and the tentorial margin using MR cisternography showed that the left side was shorter than the right side. We presumed that an isolated lateral brain stem injury was caused by the direct impact of the tentorium cerebelli. Typically the location of this type of lesion is present in the same side as that of impact. However in this case the orientation was opposite to that. We considered that the distance between the brain stem and the tentorial margin affected the mechanism of this lesion.