A case of drug-induced myopathy in alcoholic cirrhosis caused by voriconazole.

BACKGROUND: Voriconazole is a new generation of broad-spectrum antifungal agents commonly used in the treatment of invasive aspergillus infections. CASE REPORT: We reported a rare case of myopathy induced by voriconazole, which showed severe muscle pain and significantly elevated myocardial enzymes. Enzymes eventually achieved good efficacy by switching voriconazole to micafungin and the use of L-carnitine. CONCLUSIONS: This reminded us it was necessary to be vigilant for rare adverse reactions of voriconazole in the population with liver dysfunction, the elderly population, and people with multiple underlying diseases in clinical practice. During medication of voriconazole, close attention should be paid to the occurrence of adverse reactions to avoid life-threatening complications.

Isolation and purification of HSV-1 specific transfer factor produced by HSV-1 immunized goat leukocyte dialysate.

A herpes simplex virus type 1 (HSV-1)-specific transfer factor (TF), was separated and purified from the leukocyte dialysate of goats immunized with HSV-1 using affinity chromatography on antigen-sorbent and reversed phase high performance liquid chromatography (RP-HPLC). The antigen-specific activities of the starting dialysate and the isolated TF component (s) were examined by 51Cr-labelled leukocyte adherence inhibition (51Cr LAI) assay. The analytical hydrophobic interaction HPLC (HI-HPLC) and isoelectric focusing (IEF) techniques were employed to evaluate the purity and the isoelectric point (PI) of isolated TF component(s). The experiments provided a two-step procedure for purifying the TF material from the starting dialysate. It seems that the purified active TF component (PTFC) was specific for HSV-1. The specific PTFC activity was increased 10,000-fold as compared with the activity of the dialysate. The active moiety appeared as a single band in the IEF gel as demonstrated by silver staining; it was hydrophilic and its PI was pH 4.48.

Chemical characterization of the purified component of specific transfer factor in the leukocyte dialysates from HSV-1 immunized goats.

The chemical characterization of the purified component responsible for HSV-1 specific transfer factor activity (PTFC) by high resolution analytical methods was performed. PTFC had a molecular weight of 6,000 dalton by the size-exclusion HPLC analysis; it showed a marked UV-absorbance spot at 254 nm and a fluorescent spot at 366 nm on the thin-layer plate by thin-layer chromatography which spots coincided at the same place of the plate. The amino acid composition and sequencing analyses showed that PTFC consisted of at least twelve different amino acids, but the amino acid sequence could not be determined. The combined results indicate that PTFC is a compound with a molecular weight of 6,000 dalton, composed of peptide and nucleotide-like material. The peptide is rich in aspartic acid and its N-terminal end may be blocked.

Nature and antigen-specific activities of transfer factor against herpes simplex virus type 1.

Transfer factor specific for herpes simplex virus (HSV) type 1 (TFHSV-1) was prepared from splenic cells of HSV-1 immunized mice. Protection was transferred with TFHSV-1 to nonimmune mouse recipients. The TFHSV-1 injected mice had a higher survival rate after lethal HSV-1 challenge as compared to mice injected with a nonspecific transfer factor (P less than 0.05). 51Cr-labelled leukocyte adherence inhibition (51-Cr-LAI) test was used to demonstrate the specific activity of transfer factor in vitro. Only leukocytes incubated with TFHSV-1 exhibited significant adherence inhibition (P less than 0.01) to HSV-1 antigen, but not to control antigen. Specific activity component of TFHSV-1 (STFc) was separated by affinity adsorption with the antigen. Activity of STFc in 51Cr-LAI test was significantly higher than that of TFHSV-1 (P less than 0.01). Ratio activity of STFc in protective host immunity was 16 times as much as that of TFHSV-1. STFc was analysed by high performance liquid chromatography, thin layer chromatography and isoelectric focusing in the polyacrylamide gel. Results revealed that STFc appeared to be a polypeptide with a molecular weight of about 12,870 dalton.

[Effect of the tumor-bearing host serum on the leukocyte adherence inhibition reaction mediated by immune RNA].

51Cr-labelled leucocyte adherence inhibition (LAI) assay was used as an index to study the activity of xenogenic immune RNA (iRNA) in inducing normal LACA mouse spleen lymphocytes to mediate tumor specific response in vitro. RNA was extracted from the spleen and lymph nodes of the guinea pigs immunized by S180 or H22 ascitic tumor cells and from those of the normal guinea pigs. Extracts of S180 or H22 tumor cells and that of normal LACA mouse livers were prepared by PBS method respectively. Three kinds of RNA and three kinds of cell (tissue) extracts were grouped into nine combinations. A defined number of 51Cr-labelled lymphocytes was added to each group. The results showed that only in the combination of two kinds of iRNA and the corresponding tumor cell extract, adherence of normal lymphocyte was significantly inhibited. Serum from tumor bearing host inhibited LAI reaction mediated by iRNA. The "blocking" effect was specific since it occurred only when the serum and tumor extract in the reaction system were taken from the same tumor-bearing donor.

[Changes in beta-endorphin and its messenger RNA in pituitary, hypothalamus, lymphocytes and blood plasma during cold acclimation of rats].

Changes of beta-endorphin (beta-EP) and its mRNA in pituitary (P), hypothalamus (HT), lymphocytes (LC) and blood plasma (BP) during cold acclimation of SD male rats were studied by beta-EP mRNA dot blot, RP-HPLC and beta-EP radio-immunoassay (RIA). Experimental results showed: (1) After cold-exposure for 1 week pituitary beta-EP mRNA increased significantly with the appearance of stimulated cellular immune function. (2) beta-EP mRNA in hypothalamic immune center and peripheral LC increased when cold acclimation of animals was established for a cold exposure of 2 weeks (C2W). (3) From C2W onward, plasma beta-EP also continued to increase, indicating an augmented state of cellular immune function. As LC and plasma beta-EP product continued to show increase, pituitary beta-EP mRNA content recovered to control level from C2W onward possibly due to a feedback mechanism through LC-P-HT axis.

Optimal control of blood pressure can reverse left ventricular hypertrophy in uremic hypertensive hemodialysis patients.

We investigated the effects of antihypertensive treatment on left ventricular hypertrophy (LVH) of long-term hemodialysis patients. In uremic patients, it is still controversial in antihypertensive effect to the regression of LVH. The left ventricular size and function of 39 uremic hypertensive long-term hemodialysis patients (27 men, 12 women, mean age 58.3) was evaluated with M-mode, 2-dimensional and Doppler echocardiography before, and 12 months after, the start of combined antihypertensive therapy. This therapy included angiotensin II converting enzyme inhibitors, beta-blockers and calcium antagonists. Patients were classified as responders or nonresponders, depending upon whether their systolic blood pressure (SBP) decreased by more than 10 mmHg after antihypertensive treatment for 12 months. Before treatment, 36 (92%) patients had LVH and diastolic dysfunction and three (8%) had systolic dysfunction. At the end of 12 months, only 25 (64%) patients had LVH, 30 (77%) had diastolic dysfunction and 2 (5%) had systolic dysfunction. Left ventricular mass index (LVMI) also decreased from 203.63 +/- 70.47 g/m2 to 178.57 +/- 67.31 g/m2. LVMI correlated with systolic blood pressure (SBP) but did not correlate with diastolic blood pressure (DBP). There were 26 responders and 13 non-responders. Among responders, both the SBP (153.91 +/- 13.24 mmHg vs 134.43 +/- 14.21 mmHg, p < 0.01) and DBP (90.39 +/- 7.89 mmHg vs 79.98 +/- 7.35 mmHg, p < 0.01) decreased significantly after antihypertensive therapy. Responders also exhibited progressive regression of LVH (LVMI decreased significantly from 208.52 +/- 72.03 g/m2 to 168.52 +/- 55.53 g/m2, p < 0.05). However, LVH regression was not found in nonresponders (LVMI showed 194.84 +/- 64.36 g/m2 vs 193.66 +/- 77.67 g/m2). We conclude that good control of blood pressure can reverse LVH in hypertensive hemodialysis patients.

Relationship between microalbuminuria, left ventricular mass and function in essential hypertension.

To investigate the relationship of microalbuminuria, left ventricular hypertrophy and hypertension, 150 hypertensive patients were studied. All patients received a series of blood pressure (BP) measurements, overnight urine collection for microalbuminuria determination, chest radiography (CXR), electrocardiography (EKG) and echocardiographic assessment. Echocardiographic variables including left ventricular mass index (LVMI), fractional shortening (FS) and Doppler mitral flow E/A ratio were analyzed. Patients were divided into 4 groups according to diastolic blood pressure. Left ventricular hypertrophy (LVH) was identified by EKG in 28 patients (18.7%), by CXR in 56 patients (37.3%) and by echocardiography in 126 patients (89.3%). Microalbuminuria was detected in 42 patients (28%). Microalbuminuria tended to present in patients with higher systolic, diastolic and mean blood pressure. There was no relation between FS and E/A ratio and the degree of blood pressure elevation. However, there was a strong correlation between microalbuminuria and LVMI (p < 0.001), this correlation was not related to any difference in blood biochemistry. The results of this study indicate that the severity of microalbuminuria relates closely to the severity of hypertension. In addition, hypertensive patients with microalbuminuria tend to have higher LVMI.

[Human angiogenin: expression, purification, biological assay].

Angiogenin cDNA was obtained by RT-PCR, and cloned into the fusion expression vector pRSETB. The recombinant Angiogenin protein was fused with His6 at its N-terminal and expressed as inclusion body. The expression level was about 10% of the total bacteria protein. After dissolved in 8 mol/L urea, the recombinant protein was purified by Ni2(+)-NTA chelating resin, according to the high affinity of His6 with Ni2+. The biological assay indicated that purified rhANG could induced the new blood vessel formation of CAM and degraded tRNA in vitro.

High expression of tumor necrosis factor alpha cDNA in E. coli using site-specific deletion mutagenesis.

Using oligonucleotide-directed site specific mutagenesis technique, a TNF-alpha cDNA coding 157 amino acids without signal sequence and initiated with ATG was obtained. Sequencing data showed the precise deletion and insertion of the DNA fragment as designed. The modified TNF gene was expressed in E. coli with a expression vector pBV220. The expression level reached 10(8) units per liter culture. The scanning of the SDS-PAGE gel showed that the amount of the expressed TNF is about 22.8% of total soluble bacterial protein. The TNF activity can be neutralized with TNF monoclonal antibody.

Red blood cell osmotic fragility in chronically hemodialyzed patients.

Chronic renal failure induces anemia and a short erythrocyte life span. Red blood cell (RBC) osmotic fragility is the resistance of RBC hemolysis to osmotic changes that is used to evaluate RBC friability. To find the cause of shortened red cell survival in uremic patients, we evaluated the RBC osmotic fragility in 57 chronic hemodialyzed patients. Each patient had received 12 h of dialysis per week continuously prior to being enrolled in the study. Nineteen healthy volunteers served as a control group. Biochemistry, hemoglobin, electrolyte, osmolarity, beta2-microglobulin, and intact parathyroid hormone were examined before and after the dialysis session. To evaluate the osmotic fragility of RBC, blood samples were collected in heparinized test tubes. Fifty microliters of the RBC of each individual was then incubated in solutions containing a series of various concentrations of NaCl ranging from 0 to 0.6%. The concentration of NaCl at which 50% of RBCs were lysed was considered the median osmotic fragility (MOF). The results showed that the MOF was significantly greater in hemodialyzed patients before dialysis than in the control group (0.41 +/- 0.03 vs. 0.39 +/- 0.02%). The osmotic resistance to hemolysis was also recorded after dialysis (MOF 0.38 +/- 0.03%). Correlation analysis showed that the MOF was significantly correlated with urea nitrogen, serum osmolarity, and intact parathyroid hormone level. In addition, the osmotic fragility was higher in patients who had a predialysis intact parathyroid hormone level > 100 pg/dl. In conclusion, hemodialysis can improve the osmotic fragility. The mechanism underlying this improvement may be the removal of low molecular weight uremic toxins, resulting in normalization of serum osmolarity. Our results indicate that parathyroid hormone is probably a major factor influencing RBC osmotic fragility in chronic renal failure.