[Effect and safety of Lasso suture hook in transvaginal sacrospinous ligament fixation].

To investigate the feasibility and safety of the Lasso suture hook in transvaginal sacrospinous ligament fixation, a total of 38 patients with vaginal vault prolapse at or above stage Ⅱ, and aged 46-75(62.7±12.5)years, who underwent transvaginal sacrospinous ligament fixation at the Second Affiliated Hospital of Soochow University from January 2018 to January 2021 were retrospectively analyzed. After complete exposure of the right sacrospinous ligament, the cervical/uterosacral ligament was sutured to the sacrospinous ligament using Lasso hook and polypropylene sutures. The completion rate of the operation, intraoperative complications, operation time, blood loss, and postoperative situations were observed, and the objective cure rate and subjective satisfaction were followed up. Transvaginal sacrospinous ligament fixation was successfully performed in all 38 patients using Lasso suture hooks. There were no bladder or rectum injuries during the operations, and no pelvic hematoma occurred. The operation time was 15-40 (24±9.5) min; the intraoperative bleeding was 20-60 (40±12.5) ml; the visual analogue scale(VAS)score was 3-5 (3.2±1.4) points on the first day of postoperative, and 2-4 (2.2±1.8) points on the third day of postoperative. No numbness or pain in buttocks and lower limbs after the operation. The 3-month follow-up results showed that the objective surgical success rate of the postoperative pelvic organ prolapse quantitation (POP-Q) score was 100% (38/38). The 1-year follow-up results showed that the objective surgical cure rate of postoperative POP-Q score was 92.1% (35/38). The score of Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20)was 42-180(120.4±44.9)before operation and 8-75 (28.0±14.3) after operation(t=15.90, P<0.001); The score of Pelvic Floor Function Impact Questionnaire-Short Form7 (PFIQ-7) was 52-214(112.8±44.5)before operation and 5-29 (14.3±6.0) after operation (t=14.40, P<0.001), and the subjective satisfaction rate is 89.5% (34/38) conducted by Patient Global Impression of Improvement (PGI-I). Transvaginal sacrospinous ligament fixation with Lasso suture hook is simple, safe, and feasible.

[Application of transvaginal morcellation within disposable extraction bag with traction wire in laparoscopic myomectomy].

To investigate the effect and clinical value of morcellation within disposable extraction bag with traction wire through posterior vaginal fornix in laparoscopic myomectomy. A total of 42 patients who underwent laparoscopic myomectomy and morcellation through posterior vaginal fornix in the Second Affiliated Hospital of Soochow University from June 2019 to June 2021 were retrospectively analyzed. After the uterine fibroids were removed, the fibroids were placed into the extraction bag, tightening the mouth of the bag with a traction wire to make it airtight. After the uterine incisions were sutured, the extraction bag was taken out through the posterior fornix of the vagina, and the fibroids were broken up with a scalpel in the bag and taken out. The fibroids were successfully removed from the 42 patients through the posterior fornix of the vagina. There were no fibroids fragments found in the peritoneal cavity and vagina. There were no malignant cells or spindle cells found in the peritoneal lavage cytology before and after the operation. After filling the extraction bags with water, there was no leakage. There were 39 cases of uterine leiomyoma, 2 cases of cell-rich uterine leiomyoma, and 1 case of smooth muscle tumor of uncertain malignant potential in postoperative pathological diagnosis. Forty-two cases were followed up for 6 to 30 months. The posterior vaginal fornix incision healed well and there was no recurrence or metastasis. Morcellation within disposable extraction bag with traction wire through posterior vaginal fornix in laparoscopic myomectomy is a safe and feasible method for fibroids removal, which may help to reduce the dissemination of iatrogenic tumors.

[Application of morcellation through small umbilical incision in laparoscopic myomectomy].

To investigate the effect of morcellation through small umbilical incision in laparoscopic myomectomy. A total of 67 patients who underwent laparoscopic myomectomy in the Second Affiliated Hospital of Soochow University from February 2018 to October 2019 were retrospectively analyzed. Fibroids were loaded into disposable laparoscopic collection bags and then retrieved through small umbilical incision. The operation of all 67 patients were successfully completed. There were no leakage of collection bags or fibroids fragments found in the peritoneal cavity and the puncture holes. There were no spindle cells or malignant cells found in the peritoneal lavage cytology before and after operation. There were 64 cases of uterine leiomyoma, 2 cases of cellular leiomyoma, and 1 case of leiomyoma with cystic degeneration in postoperative pathological diagnosis. The weight of fibroid was 110-420 (227±106) g; the operation time was 58-274 (107±45) min; the time for retrieving specimen was 8-27 (18.4±10.6) min; the time for suturing umbilical incision was 4-11 (7.8±4.6) min; the score of pain numeric rating scale (NRS) at 24 h, 48 h, 72 h after operation was 4-6 (4.5±1.2) points, 2-4 (2.7±1.1) points, and 1-2 (1.6±0.4) points, respectively; the Hollander wound evaluation score was 3-5 (4.6±0.5) points. The umbilical incisions looked and healed well after operation. Morcellation through small umbilical incision in laparoscopic myomectomy is a safe and practical method of specimen removal, which may help to reduce the dissemination of iatrogenic tumors.

FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats.

OBJECTIVE: Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. MATERIALS AND METHODS: Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. RESULTS: Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. CONCLUSIONS: FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.

STMN1 in colon cancer: expression and prognosis in Chinese patients.

OBJECTIVE: To study the stathmin (STMN1) expression in colorectal cancer and tumor-adjacent normal tissue and discuss its prognostic significance in colon cancer. PATIENTS AND METHODS: STMN1 was tested with qRT-PCR in 30 samples of fresh colon cancer tissue and tumor-adjacent issue, and with immunohistochemical SP method in 105 samples of fresh colon cancer tissue and tumor-adjacent issue to analyze the association between its expression and clinical pathological parameters. Clinical data was combined to study the relationship between STMN1 expression and 5-year survival rate. Univariate analysis and Cox multivariate regression were performed to study the correlation between STMN1 expression and prognosis. RESULTS: The mRNA and protein level of STMN1 were significantly higher in colon cancer samples than tumor-adjacent normal tissues (p<0.05). STMN1 expression was independent of patient age, gender or location, but significantly related to lymph node metastasis and TNM staging (p<0.05). Survival analysis by Kaplan-Meier method showed that STMN1 expression was significantly related with the survival of colon cancer patients. The median survival time of STMN1-positive patients (37.5 months) was significantly shorter than STMN1-negative patients (57.1 months, p<0.05). Cox multivariate regression indicated that STMN1 is independent prognostic factors predicting the development, invasion and metastasis of colon cancer (p<0.05). CONCLUSIONS: STMN1 overexpression in colon cancer is independently associated with improved survival and significantly related to the development of the disease. Our findings suggest that presence of a STMN1-prognosis interaction that potentially determines clinical outcome.

An effective approach to achieving low supersaturation for a/b-axis oriented YBa(2)Cu(3)O(7-δ) film growth.

Using liquid phase epitaxy, a novel approach was developed to grow a-axis oriented YBa2Cu3O7-δ films (a-films) under an air atmosphere, which has been difficult previously since its formation requires extremely low supersaturation. In our new method, instead of conventional cooling from the saturated to supersaturated state, an extremely small driving force for film growth was generated from the unsaturated through saturated to supersaturated state. By controlling the amount of fresh solvent and the melting time before cooling down the Y-Ba-Cu-O solution, a growth region width up to 30 K was acquired for preparing a-films. Significantly, this work provides a low-cost and convenient way to produce high-quality a-films, which are potentially suitable for Josephson junction devices.

Amphotericin B colloidal dispersion: an improved antifungal therapy.

Amphotericin B colloidal dispersion (ABCD) is a near 1:1 discoidal complex of amphotericin B (AMB) and sodium cholesteryl sulfate (SCS) arranged as a bilayer of SCS interspersed with AMB via noncovalent interactions. The complex is stable in blood and plasma with minimal dissociation. In vitro and in vivo studies show that ABCD is as effective and four to five times safer than conventional AMB (CAB) for fungal infection. Compared with CAB treatment, ABCD demonstrates reduced peak plasma levels, prolonged residence time, and lowered AMB levels in most tissues including kidney, the major target of toxicity for CAB. In 572 patients with systemic fungal infections secondary to severe underlying disease, ABCD doses < or = 6 mg/kg/day were well tolerated, even in those who failed to tolerate or respond to CAB. Mild-to-moderate, dose-dependent, infusion-related adverse events typically seen with CAB were also observed with ABCD, with no sign of renal or hepatic toxicity. Complete or partial recovery was seen in 57.3%. Therefore, ABCD should be considered as an alternative treatment of systemic fungal infections.

Behavioral and endocrine response to cholecystokinin tetrapeptide in patients with posttraumatic stress disorder.

BACKGROUND: Given the relationship between posttraumatic stress disorder (PTSD) and panic, it was of interest to examine whether panic provoking agents affect PTSD symptoms. We therefore investigated the behavioral and endocrine response of PTSD patients to the panicogen cholecystokinin tetrapeptide (CCK-4). METHODS: Eight patients with PTSD (DSM-IV) received 50 micrograms CCK-4 intravenously in a placebo-controlled, double-blind balanced design. Provocation of panic, anxiety, and flashbacks was assessed. Plasma adrenocorticotropin (ACTH) and cortisol levels after CCK-4 were measured and compared to healthy subjects matched for age, gender, and provoked symptoms. RESULTS: Despite significant effects of CCK-4 on anxiety and panic symptoms, no significant provocation of flashbacks emerged. CCK-4-induced panic symptoms showed an inverse correlation to trait dissociation. The ACTH response after CCK-4 was significantly lower in PTSD patients than in controls. Cortisol was similarly increased in both groups after CCK-4, but PTSD patients showed a more rapid decrease of stimulated cortisol concentrations. CONCLUSIONS: Panic symptoms or heightened anxiety are not necessarily conditioned stimuli for the provocation of posttraumatic flashbacks. Further studies in PTSD with different panicogens should be controlled for the potential interference of trait dissociation. Our hormone data show further evidence for a corticotropin-releasing hormone (CRH) overdrive and enhanced negative glucocorticoid feedback in PTSD patients.

Anti-HIV activity of amphotericin B-cholesteryl sulfate colloidal dispersion in vitro.

We examined whether the anti-HIV-1 activity of the polyene antibiotic Amphotericin B (AMB) is retained following incorporation into sterically stabilized 'Stealth' liposomes (L-AMB) with prolonged circulation in vivo, or cholesteryl sulfate colloidal dispersions (CD-AMB). The effects of the different preparations on acute infection of H9 cells with HIV-1IIIB, spreading of the virus from chronically infected H9/HTLV-IIIB cells to SupT1 cells, and HIV-1-induced syncytium formation were evaluated. Infection was monitored by p24 levels in culture supernatants. L-AMB did not affect HIV-1 infection. When present only during initial infection, AMB (3-20 microg/ml) reduced p24 levels by 70-80% after 7 and 10 days post-infection, while CD-AMB inhibited p24 production by approximately 30-40% at day 7 and 50-60% at day 10. The inhibitory effect of CD-AMB and AMB was enhanced by continuous treatment of acutely infected cells. The reduction of p24 production during continuous treatment was not due to cytotoxicity. During spreading of infection from infected to uninfected cells, AMB almost completely inhibited virus production while CD-AMB reduced both p24 production and the cytopathic effect in a dose-dependent manner. HIV-1 induced syncytium formation was slightly inhibited by AMB but not by CD-AMB. Because CD-AMB is considerably less cytotoxic than AMB, its ability to inhibit HIV infection in vivo needs to be evaluated further.

Sterically stabilized pH-sensitive liposomes. Intracellular delivery of aqueous contents and prolonged circulation in vivo.

Liposomes that destabilize at mildly acidic pH are efficient tools for delivering water-soluble drugs into the cell cytoplasm. However, their use in vivo is limited because of their rapid uptake from circulation by the reticuloendothelial system. Lipid-anchored polyethylene glycol (PEG-PE) prolongs the circulation time of liposomes by steric stabilization. We have found that addition of PEG-PE to the membrane of pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and dioleoylphosphatidylethanolamine (DOPE) confers steric stability to these vesicles. This modification significantly decreases the pH-dependent release of a charged water-soluble fluorophore, calcein, from liposomes suspended in buffer or cell culture medium. However, the ability of such liposomes to release calcein intracellularly, measured by a novel flow cytometry technique involving dual fluorescence labeling, remains unaltered. As expected, the release of calcein from liposomes endocytosed by cells is inhibited upon pretreatment of the cells with NH4Cl, an inhibitor of endosome acidification. The unique properties of these liposomes were also demonstrated in vivo. The distribution kinetics of 111In-containing CHEMS/DOPE/PEG-PE liposomes injected intravenously into rats has pharmacokinetic parameters similar to control, non-pH-sensitive, sterically stabilized CHEMS/distearoylphosphatidylcholine/PEG-PE liposomes. In contrast, regular pH-sensitive liposomes lacking the PEG-PE component are cleared rapidly. Sterically stabilized pH-sensitive liposomes may therefore be useful for the intracellular delivery in vivo of highly negatively charged molecules such as genes, antisense oligonucleotides, and ribozymes for the treatment of various diseases.

Increased pituitary activation following metyrapone administration in post-traumatic stress disorder.

Our previous findings have demonstrated that individuals with post-traumatic stress disorder (PTSD) show lower basal cortisol levels, a larger number of lymphocyte glucocorticoid receptors, and an enhanced suppression of cortisol following the administration of dexamethasone compared to normals and patients with major depression. We have previously suggested that these alterations reflect an enhanced negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD. However, in the absence of direct knowledge of pituitary capability in this disorder, it has been equally likely that the alterations observed reflected either pituitary or adrenal insufficiency. In the present study, we examined ACTH release from the pituitary gland in PTSD following the administration of metyrapone. Metyrapone resulted in a significantly greater increase of ACTH and 11-deoxycortisol in combat veterans with PTSD (n = 11) compared with normal male volunteers (n = 8). When seen in the context of other abnormalities observed in PTSD, the present demonstration of increased pituitary activity in the absence of negative feedback provides unequivocal support for the hypothesis of enhanced negative feedback.

Cardioprotection by liposome-conjugated sialyl Lewisx-oligosaccharide in myocardial ischaemia and reperfusion injury.

OBJECTIVES: Selectins are important adhesion molecules which utilize a carbohydrate ligand such as sialyl Lewisx (SLex). Our objective was to study the effects of a liposome-conjugated SLex (Lipo-SLex) in myocardial ischaemia (MI) and reperfusion (R) injury in order to further clarify the actions of this carbohydrate. METHODS: We studied the efficacy of Lipo-SLex in a feline model of MI (90 min) and R (270 min) injury in vivo. Lipo-SLex (400 micrograms SLex/kg, iv) was administered intravenously 10 min prior to R. We also utilized an in vitro system of neutrophil adherence to thrombin-stimulated coronary endothelium to validate the efficacy of Lipo-SLex. RESULTS: Lipo-SLex significantly attenuated myocardial necrosis (8.6 +/- 1.2 vs. 29.5 +/- 3.1% of area-at-risk, P < 0.01) and plasma creatine kinase activities (P < 0.01) compared to vehicle (liposome alone). Moreover, endothelium-dependent relaxation to acetylcholine and A23187 in ischaemic-reperfused coronary rings obtained from cats treated with Lipo-SLex was significantly preserved compared to cats given liposomes without SLex (P < 0.01). After reperfusion, ex vivo PMN adherence to ischaemic-reperfused coronary endothelium was significantly increased in vehicle-treated cats, however, this was significantly attenuated in Lipo-SLex-treated cats (82 +/- 7 vs. 28 +/- 3 PMNs/mm2, P < 0.01). Myeloperoxidase activity in the ischaemic myocardium, a marker of PMN accumulation, was also significantly attenuated in Lipo-SLex-treated cats compared to liposomes without SLex (P < 0.01). CONCLUSIONS: Liposome-conjugated SLex-oligosaccharide attenuates myocardial necrosis and preserves coronary endothelial function following MI/R in vivo. The mechanism appears to be mediated by inhibition of the initial PMN-endothelial interaction and eventual accumulation into the ischaemic cardiac tissue. The liposome-SLex complex may be an efficient drug formulation for acute inflammatory diseases.

Comparative tissue distribution and elimination of amphotericin B colloidal dispersion (Amphocil) and Fungizone after repeated dosing in rats.

The pharmacokinetic profiles of amphotericin B (AmB) after administration of Amphocil, an AmB/cholesteryl sulfate colloidal dispersion (ABCD) and the micellar AmB/deoxycholate (Fungizone) were compared after repeated dosing in rats. After administration of ABCD and Fungizone at an equal AmB dose (1 mg/kg), AmB concentrations in plasma and most tissues were lower for the ABCD dose, especially in the kidneys where reduced drug concentration correlated with reduced nephrotoxicity. In contrast, AmB concentrations in the liver were substantially higher when ABCD was administered; however, without an accompanying increase in hepatotoxicity. Daily administration of ABCD for 14 days did not lead to AmB accumulation in plasma; while a slight accumulation was observed after multiple administration of Fungizone. AmB was eliminated more slowly from the plasma and various tissues and urinary and fecal recoveries of AmB were reduced after ABCD administration. These results suggest that ABCD may be stored in tissues in a form that is less toxic and is eliminated from the systemic circulation by a different mechanism than the free and protein-bound AmB in plasma. AmB accumulation in the spleen was observed when higher, doses of ABCD (5 mg/kg) were administered, which could be due to saturation of hepatic uptake of AmB. Comparison of spleen concentrations of AmB between ABCD and Fungizone at 5 mg/kg AmB doses was not possible because of Fungizone's toxicity in rats. In all other organs, AmB concentrations reached or approached a steady state within two weeks of dosing with ABCD. Urinary and fecal clearences of AmB were not different between ABCD and Fungizone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection.

The development of long-circulating liposomes containing lipid derivatives of poly(ethylene glycol) (PEG), termed Stealth liposomes, has considerably improved the prospects for therapeutic applications of liposomal drug delivery systems. We have examined the pharmacokinetics and biodistribution of long-circulating, as compared to conventional, liposomes after subcutaneous (sc) administration in mice. Results obtained after subcutaneous administration were compared to those obtained after intravenous (iv) and intraperitoneal (ip) administration. Liposomes, following sc administration, appeared intact in the circulation subsequent to moving down the lymph node chains that drain the site of injection. Liposomes containing PEG-distearoylphosphatidylethanolamine (PEG-DSPE) resulted in the highest levels of small (80-90 nm) liposomes in the blood, with up to 30% of vivo label appearing in the blood at 12 to 24 h post-injection. In the absence PEG-DSPE approx. 4-fold lower levels of liposomes were found in the blood. Small size of the liposomes was critical to their ability to move into the circulation, with liposomes above 110-120 nm not appearing in blood to any significant extent. The presence of PEG-DSPE and cholesterol was important for the in vivo stability of the liposome after sc administration. Although liposome levels were significantly higher in the draining lymph nodes after sc administration, levels associated with other tissues were proportionately reduced relative to the iv and ip routes of administration. Liposomes appeared in blood after ip and sc administration with half-lives of approx. 0.6 and 9 h, respectively, and subsequent to appearing in blood had similar biodistribution, pharmacokinetics and half-lives (20.4 h) to liposomes given by the iv route.

Antibodies to hepatitis C virus and hepatitis C virus RNA in Chinese blood donors determined by ELISA, recombinant immunoblot assay and polymerase chain reaction.

Antibodies to hepatitis C virus (anti-HCV) were determined in Chinese blood donors from the city of Wuhan by ELISA screening tests and confirmatory recombinant immunoblot assay (RIBA). 281 and 222 sera were sampled under similar conditions in 1989 and 1990, respectively. The first collection of sera was sent to Sweden in lyophilized form, the second directly as fresh, unfrozen sera. A high proportion (22%) of the lyophilized sera were positive in the screening assay but only 6 (2.10%) were positive by RIBA with antibodies against both the C100-3 and 5-1-1 peptides. HCV RNA could be detected by polymerase chain reaction (PCR) analysis in 3 of the 6 sera and in one reacting with C100-3 only. In the second material of fresh sera only 3 were positive in the screening anti-HCV ELISA, but none was RIBA or PCR positive. Thus, the overall prevalence of anti-HCV among the 503 Chinese blood donors as identified by RIBA was 1.2%, and that of HCV RNA by PCR was 0.8%. The confirmed antibody prevalence is higher than that reported in the western literature.

Hepatitis B virus DNA detected by PCR in sera and liver tissues of Chinese patients with chronic liver diseases.

To investigate the HBV infection and its replication in Chinese patients with chronic liver disease, polymerase chain reaction (PCR) was employed to detect hepatitis B virus DNA in sera of 410 patients with chronic liver disease and liver samples from 188 patients. The HBV DNA detectability in all serum samples was 58%. Among them 100% HBeAg-positive and 58% anti-HBe cases were HBV DNA detectable respectively. However, HBV DNA was also found in 23% HBsAg-negative/anti-HBc positive chronic cases. Furthermore, 30% anti-HBs positive chronic cases who had neutralizing antibody against HBV infection, continued to contain HBV DNA. Our findings indicate that HBV infection and its replication are dominant cause of chronic liver disease and some HBV variants may escape from the protective antibody to induce chronic liver disease, even anti-HBs antibody circulated.

Hepatitis C virus infection: its role in chronic liver diseases.

In order to find out the infectious rate of hepatitis C virus (HCV) among chronic liver diseases, we investigated antibodies against hepatitis C virus and HCVRNA by method of ELISA, RIBA and RT-PCR in 410 patients with chronic liver disease. The prevalence of HCV infection was found to be 4%. Whereas the positive rate of HBsAg and HBV-DNA of these cases was 69% and 58%, respectively. There is no statistical significance between HCV infectious rate of patients with positive and negative HBsAg. The relative low infectious rate of HCV infection among chronic hepatic diseases indicates that HBV infection plays a more important role in causing chronic hepatitis than that of HCV. Thus, special emphasis should be paid to the preventive and therapeutic measures against hepatitis B in China.

Establishment and application of SPA-co-operated ELISA for detection of anti-HCV-IgM.

A staphylococcus aureus protein A co-operated ELISA (SPA-ELISA) for the detection of anti-HCV-IgM has been established using HCV antigenic polypeptide, SPA-bearing germs and horseradish peroxidase labelled anti-human IgM. The specificity of SPA-ELISA has been confirmed by some substitution tests, blocking tests and destroying test with 2-mercaptoethanol. The results showed that the rate of anti-HCV-IgG in a group of patients with acute hepatitis and there were significant difference in anti-HCV-IgM was higher than that of anti-HCV-IgM detected rates between patients with acute hepatitis and those with chronic hepatitis (32.26%, P < 0.01). On the other hand, the positive rates of anti-HCV-IgM were 53.66% and 63.41% in transfusion associated hepatitis, 38.10% and 42.86% in sporadic hepatitis, 6.11% and 16.33% in people who have had active social activities, 40.00% and 10.00% in a group of blood donors respectively. Furthermore, taking into account the characteristics of HCV polypeptide used, its easiness of manipulation, and elimination of the interference of anti-HCV-IgG in sera, the new SPA-ELISA is believed to be of practical value in clinical and epidemiological studies of hepatitis C.

Relationship of pharmacokinetics and drug distribution in tissue to increased safety of amphotericin B colloidal dispersion in dogs.

The safety, pharmacokinetics, and distribution in tissue of an amphotericin B (AmB)-cholesteryl sulfate colloidal dispersion (ABCD) were compared with those of micellar amphotericin B-deoxycholate (m-AmB). Dogs received 14 daily injections of ABCD (0.6 to 10 mg/kg of body weight per day) or m-AmB (0.6 mg/kg/day). Safety was evaluated by monitoring body weight, hematology, clinical chemistry, and urinalysis during the study and by microscopic examination of tissues at the time of necropsy (day 16). AmB concentrations in plasma were measured in some groups on days 1, 7, and 14 and in necropsy tissue samples. ABCD produced a spectrum of toxic effects in the kidneys, gut, and liver similar to those of m-AmB, but ABCD was eightfold safer than m-AmB. The highest tolerated dose of ABCD (5.0 mg/kg/day) produced effects similar to those of m-AmB (0.6 mg/kg/day). ABCD produced lower concentrations in plasma than an equal dose of m-AmB did. Clearances on days 7 and 14 were higher for ABCD (304 and 295 ml/h.kg) than they were for m-AmB (67 and 53 ml/h.kg). Concentrations in plasma reached steady state after ABCD administration, but they increased after repeated dosing with m-AmB. Diurnal fluctuations in AmB concentrations in plasma were observed 4 to 8 h after the time of dosing. ABCD resulted in lower AmB concentrations in tissue than m-AmB did, except in the reticuloendothelial system. Up to 90% of AmB administered as ABCD was recovered from the liver and spleen on day 16. Reduced drug levels in the kidneys and gut correlated with reduced indications of toxicity in these organs after ABCD administration. Although ABCD increased concentrations of AmB in the reticuloendothelial system, increased toxicity was not observed in these organs.

Analysis of antigenic polypeptides of Dane particles and antibody response ability of HBV infected subjects to PreS1 polypeptides.

We demonstrated the constitutive polypeptides (PP) of Dane particles employing Western Blot and investigated the antibody response ability of HBV infected subjects to PreS1 PP in comparison with other serum markers from HBV infected individuals. The results indicated that 1) the major reason for discrepant results may be related to the detergents used in the sample solutions and the degree of denaturation the samples had undergone; 2) there are 12 bands in the PAGE-graph of Dane particles. By Western Blot it was confirmed that 5 PP (P24, P27, P36, P39, P42) are derived from S-open reading frame (S-ORF), P21 is associated with C-ORF, P24-25 possesses some epitopes of Pol protein, and P45 and P76 express similar epitopes to human IgG and IgM; and 3) the prevalence of anti-PreS1 PP was 17.24% in the group of healthy persons following latent HBV infection, much higher than that of HBV infected patients (1.21%). The above findings imply that antibody response ability of the host to PreS1 PP is attributing to the outcome of HBV infection. It may play an important role in the elimination of the virus.