Effects of different drainage methods on serum bile acid and hepatocyte apoptosis and regeneration after partial hepatectomy in rats with obstructive jaundice.

The aim of this study was to investigate the mechanism of hepatocyte apoptosis and regeneration after partial hepatectomy in obstructive jaundice (OJ) rats under different drainage methods of bile acid intervention. Forty male Sprague Dawley rats were randomly divided into five groups. An OJ rat model was established by the following protocols. Seven days after obstruction, an SD rats model with 70% partial hepatectomy was established by different drainage methods of OJ. Blood and liver tissue samples were collected from rats 72 h after surgery; 72 h after partial hepatectomy (PH), the liver regeneration rate, the expression of proliferating cell nuclear antigen (PCNA) and the level of mitotic index (MI) in the internal biliary drainage (IBD) group were higher than those in external biliary drainage (EBD) group (P less than 0.05). Those in the EBD group were higher compared to the OJ group (P less than 0.05). There was no significant difference among the IBD group, EBD+CA group and (SO) sham operation group (P>0.05). Bax expressions had the same trend as AI in the five groups. The expression of Bcl-2 was increased in the IBD group and EBD+CA group, which was statistically higher compared to the SO group (P less than 0.05). In conclusion, both internal and external drainage can relieve biliary obstruction. The difference in liver regeneration caused by external drainage and internal drainage may be attributed to the destruction of bile acid enterohepatic circulation, which increases hepatocyte apoptosis and affects liver regeneration.

Repeated whole-lung lavage for unremitting pulmonary alveolar proteinosis: a eight-year follow-up of a case.

Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome that was first described in 1958. To date, whole-lung lavage (WLL) is still the gold-standard therapy for PAP. Herein, we report the case of a male patient who was diagnosed with PAP by open-lung biopsy 8 years prior to presentation at our clinic. The man underwent his first WLL in 2004 and showed marked clinical and radiological improvement after the operation. However, after his original presentation, proteinaceous material continued to accumulate in his lungs. Lavage was performed four additional times, but these attempts failed to arrest the decline in pulmonary function. Each lavage resulted in significant, although transient, clinical improvement.

Fragmentation mechanisms for methane induced by 55 eV, 75 eV, and 100 eV electron impact.

The fragmentation of CH4 (2+) dications following 55 eV, 75 eV, and 100 eV electron impact double ionization of methane was studied using a cold target recoil-ion momentum spectroscopy. From the measured momentum of each recoil ion, the momentum of the neutral particles has been deduced and the kinetic energy release distribution for the different fragmentation channels has been obtained. The doubly charged molecular ions break up into three or more fragments in one or two-step processes, resulting in different signatures in the data. We observed the fragmentation of CH4 (2+) dications through different mechanisms according to the momentum of the neutral particles. For example, our result shows that there are three reaction channels to form CH2 (+), H(+), and H, one synchronous concerted reaction channel and two two-step reaction channels. For even more complicated fragmentation processes of CH4 (2+) dications, the fragmentation mechanism can still be identified in the present measurements. The slopes of the peak in the ion-ion coincidence spectra were also estimated here, as they are also related to the fragmentation mechanism.

Acute toxicity of a single dose DATR, recombinant soluble human TRAIL mutant, in rodents and crab-eating macaques.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to possess activity of inducing apoptosis in variety of tumor cells in preclinical models. Several mutational versions of TRAIL have been studied as promising agents for cancer therapy and the recombinant soluble human TRAIL mutant (DATR) is one of them. The objective of the present study was to provide possible toxic target organs and proposal non-toxic dose level of DATR for clinical usage. Rodents and crab-eating macaques were used to estimate potential adverse effects of DATR following a single dose administration. The median lethal dose (LD(50)) of intravenous injection to rats and mice was determined as 262.0 and 1018.0 mg/kg b.w., respectively. The LD(50) of intraperitoneal administration to mice was found to be 1432.1 mg/kg b.w. The main changes in macaques were found in the following aspects. Hematology analysis revealed an obvious decrease of red blood cell count (RBC), hemoglobin (HB) and hematocrit (HCT) after injection. Serum biochemical analysis showed an apparent increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN) and creatinine (Crea). Furthermore, inflammatory cell infiltrate in liver and kidney was found by microscope. All the disorders suggested that liver, renal and hematological systems might be the target effectors of toxic effect induced by DATR. Based on the results of this study, the no observed-adverse-effect level (NOAEL) and the lowest observed-adverse-effect level of DATR in macaques are 90.0 and 135.0 mg/kg b.w., respectively.

The effect of the increasing prevalence of maternal obesity on perinatal morbidity.

OBJECTIVE: In this study, we assessed the temporal trends and relative and attributable perinatal risks of maternal obesity over a 20-year period. STUDY DESIGN: We conducted a retrospective cohort study between 1980 and 1999 by using a computerized perinatal database of all women who received prenatal care and delivered their infants within a regional health care system. The main outcome measures were as follows: (1) annual mean body weight and the percentage of women classified as obese at the first prenatal visit (primary definition > or = 200 lb; secondary definitions > or = 250 lb, > or = 300 lb, body mass index > 29 kg/m(2)); and (2) relative and attributable risks of obesity for selected maternal and perinatal morbidities in successive 5-year periods. RESULTS: From 1980 to 1999, the mean maternal weight of women at the first prenatal visit increased 20% (144-172 lb), as did the percentage of women > or = 200 lb (7.3-24.4), the percentage > or = 250 lb (1.9-10.7), the percentage > or = 300 lb (0.5-4.9), and the percentage with a body mass index > 29 kg/m(2) (16.3-36.4), P < .01 for all. Controlling for maternal age, race, and smoking status, obese women were at increased risk at each period for cesarean delivery (range of adjusted relative risk, 1.5-1.8), gestational diabetes (range, 1.8-2.9), and large (> 90th percentile) for gestational age infants (range, 1.8-2.2). From the earliest 5-year period (1980-1984) to the most recent (1995-1999), the percentage of obesity-attributable cesarean deliveries more than tripled from 3.9 to 11.6. Similar percentage increases were observed for the obesity-attributable risks for gestational diabetes (12.8-29.6) and large for gestational age infants (6.5-19.1). Trends for secondary obesity definitions were similar, although the magnitude of the increased attributable risks was smaller. CONCLUSIONS: Efforts to reduce the frequency of certain perinatal morbidities will be constrained unless effective measures to prevent, or limit the risks of, maternal obesity are developed and implemented.

Lethal pulmonary hypoplasia after in-utero myelomeningocele repair.

BACKGROUND: In-utero surgical repair of fetal myelomeningocele has been performed as a means to improve the postnatal condition of affected infants. CASE: A nulliparous woman underwent in-utero surgical repair of a fetal lumbosacral myelomeningocele at 24 weeks' gestation. Her postoperative convalescence was complicated by pulmonary edema, abdominal pain, chronic oligohydramnios, and preterm labor. The infant was delivered by cesarean at 33 weeks' gestation, but expired from respiratory distress caused by pulmonary hypoplasia at 9 hours of age. CONCLUSION: Until the benefits of in-utero repair of fetal myelomeningoceles are determined by well-controlled clinical trials, this technique remains investigational. Physicians and their patients who are considering this procedure must be fully aware of the potential risks that can occur.

Midtrimester vaginal Mycoplasma genitalium in women with subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the midtrimester prevalence of Mycoplasma genitalium in women who had subsequent spontaneous preterm birth. STUDY DESIGN: In a prospective study of lower genital tract infections, we identified 127 women who subsequently had spontaneous preterm birth. Vaginal samples were obtained between 21 and 25 weeks' gestation for pH, for bacterial vaginosis Gram stain, and cultures that yielded Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. M genitalium was identified by using validated polymerase chain reaction (PCR) primers, and the results were compared to pregnancy outcomes. RESULTS: Of 124 women with spontaneous preterm births, only five (3.9%) had PCR assays positive forM genitalium. The mean +/- SD delivery gestational age was similar for women with a positive PCR (34.6 +/- 2.2 weeks) and a negative PCR (34.0 +/- 2.7 weeks) (P =.62). None of the women with positive PCR results tested positive for any other sexually transmitted disease, whereas 36 (30%) women with negative PCR results tested positive. CONCLUSIONS: The occurrence of M genitalium in the vagina at midtrimester is infrequent in women with subsequent spontaneous preterm birth.

Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women.

OBJECTIVE: To relate vaginal fetal fibronectin levels in women with symptoms of preterm labor to subsequent spontaneous preterm birth. METHODS: Quantitative fetal fibronectin values were calculated from women who participated in two prospective multicenter trials relating fetal fibronectin to subsequent spontaneous preterm birth. The study populations consisted of women who presented with symptoms of preterm labor between 24(0)/(7) and 34(6)/(7) weeks, a singleton pregnancy, intact membranes, no prior tocolysis, and cervical dilation less than 3 cm. RESULTS: The characteristics of the two study populations were similar. In both populations, the rates of delivery within 7, 14, and 21 days after sampling were clustered into three distinct fetal fibronectin groups (less than 40, 40-100, and 100 ng/mL or more). As fetal fibronectin values increased, the risk of subsequent spontaneous preterm birth also increased. Delivery within 7 days of sampling was 0.4%, 3.3%, and 18.2% (trial A) and 1.4%, 8.0%, 30.0% (trial B) as the fetal fibronectin levels increased from less than 40 ng/mL, to 40-100 ng/mL, and to at least 100 ng/mL, respectively. CONCLUSION: In women with symptoms of preterm labor, an increase in fetal fibronectin from under 40 ng/mL, to 40-100 ng/mL, to at least 100 ng/mL was associated with a progressive increase in the risk of subsequent spontaneous preterm birth. The use of a single fetal fibronectin cutoff of 50 ng/mL for defining a positive test in women with symptoms of preterm labor should be reevaluated.

Current concepts on the pathogenesis and markers of preterm births.

Preterm births remain a major cause of neonatal morbidity and mortality despite our efforts over the past several decades. Our improved understanding of the complex mechanisms surrounding preterm labor, however, has resulted in the development of numerous biologic and clinical predictors of spontaneous preterm births. These developments offer the exciting prospect for the creation of specific interventions that are directed toward the various pathways involved with preterm births.

Long-term toxicity of modified recombinant human tumor necrosis factor in Macaca mulatta.

AIM: To study the long-term toxicity of modified recombinant human tumor necrosis factor (rhTNF-NC) in Macaca mulatta compared with recombinant human tumor necrosis factor (rhTNF). METHODS: rhTNF-NC 93, 9.3 GU/m2, and rhTNF 62 GU/m2 were injected i.v. daily to 16 Macaca mulatta for 1 month and 10 d, respectively. Hematologic, chemical, urinalysis values, ECG, specific antibody, bone marrow, and pathologic profile of organs were measured. RESULTS: No more adverse effects of rhTNF-NC were found in spite of anorexia in 4 monkeys and palpebral edema in 2 monkeys of 93 GU/m2 group. Besides, in rhTNF group, the injury of liver and kidneys, the decrease of erythron, the phlebitis, and thrombosis at injection site occurred. Both drugs caused the production of specific antibody. CONCLUSION: No serious adverse effects of rhTNF-NC were found in Macaca mulatta. The toxicity of rhTNF-NC was much lower than that of rhTNF.

[Effect of human inhibin alpha-fragments and monoaminergic neurotransmitters on progesterone(P4) production by corpus luteum(CL) of rat in vitro].

The effects of exogenenous monoaminergic neurotransmitters (norepinephrine, NE; epinephrine, E; dopamine, DA and 5-HT) and inhibin alpha N-terminal fragments P32 (1-32), P32-Tyr on P4 production by incubated rat CL cells were studied. The results demonstrated that: (1) alpha fragments caused significant inhibition on P4 production. (2) 0.1 mmol/L NE (or E) and 10 mumol/L DA produced a marked increase in both basal and hCG induced P4 production by CL cells (P < 0.001). The rank orders of potency of the catecholamines in stimulating P4 production were different, for basal P4 production, NE > E > DA; but for hCG induced P4 production, DA > E > NE, i.e. the order just reversed. Addition of P32-Tyr significantly neutrolized the stimulatory action of E, but only slightly increased the action of NE. (3) alpha receptor blocker phentolamine and beta receptor blocker propranolol were effective in decreasing basal and hCG-induced P4 production, the latter being more effective than the former. It was further shown that both blockers augmented the inhibitory effect of alpha-fragments on P4 production. (4) Unlike NE, E, and DA, 5-HT at 0.5 mumol/L exerted inhibitory effect on the basal and hCG-induced P4 production, but profoundly supressed the inhibitory effect of alpha-fragments on P4 production. The above results suggested: (1) Adrenergic, DA and 5-HT receptors are present in rat CL, where catecholamine might exert a stimulating effect on basal and hCG-induced P4 production via different pathways. (2) The inhibitory effect of P32, P32-Tyr on P4 production might be related to their inhibition by partial blocking alpha/beta receptors, which were antagnized by 5-HT. (3) The action of P32, P32-TYr on P4 production is brought on the participation of neurotransmitters NE, E, DA and 5-HT.

Toxicity of human recombinant interferon-gamma in rats and dogs.

AIM: To study the acute and chronic toxicities of human recombinant interferon-gamma (Hu-rIFN-gamma) in mice, rats, and dogs. METHOD: Twenty mice were administrated Hu-rIFN-gamma (i.m. or i.v.) 4.4 x 10(9) IU m-2 to observe the acute toxicity. In chronic studies, 1 x 10(7), 5 x 10(7), 1 x 10(8) IU m-2 d-1 were given to 80 rats and 5 x 10(5), 5 x 10(7) IU m-2 d-1 were injected to 14 dogs i.m. for 3 months, treatment-related changes were measured in the hematologic, chemical, urinalysis values, ECG and pathologic profile of organs and tissues. RESULTS: The maximal tolerance dose (MTD) i.m. or i.v. in mice was 4.4 x 10(9) IU m-2, 4400 times the recommended clinical dosage (1 x 10(6) IU m-2). No adverse effects were found in chronic toxicity studies. CONCLUSION: Human recombinant interferon-gamma did not produce toxic reaction in rats and dogs.

[Synthesis of tyrosine-related peptide and their effect on progesterone production].

Twenty peptides containing hydroxy-amino acids have been synthesized manually by stepwise solid-phase procedure. The chloromethyl resin and MBHA resin were used as solid supports. A new reagent of 0.5 mol.L-1 DDSi/1.5 mol.L-1 phenol/DCM was applied for the removal of N alpha-Boc group. TFMSA was the cleaving reagent. After purification by C-18 column; all products were assayed according to amino acid analysis. The bioactivity of synthetic peptides was tested for the effect on progesterone production in vitro. Eight peptides, GlyTyrAlaLys, (SarSer)2Lys and its methyl ester, TyrLys, HisTyr-NH2, ThrProTyrLys-NH2 TyrThrProArgLys and AspHisProThrPheLys showed significant effect on inhibiting hCG-induced progesterone production, and first three of them could also inhibit basal progesterone secretion. However, peptide GlySerTyr exhibited stimulative activity on basal progesterone secretion. So far, no reasonable relationship between structure and bioactivity was found.

[Synthesis of porcine brain natriuretic peptide (BNP-26) and an analog].

The porcine brain natriuretic peptide (BNP-26) and its analog, (Mpr4,D-Ala6,13) BNP(4-24)-NH2, were synthesized by solid phase method employing the Boc strategy. After HF cleavage to remove the protected groups, the crude linear peptide was air-oxidized under alkaline conditions to form the disulfide bridge. The synthetic peptides, purified by gel filtration and HPLC, were proved to have pharmacological spectra very similar to that of natural BNP such as natriuretic/diuretic, hypotensive and vaso-relaxant activities.

[Syntheses and preliminary bioassays of inhibin segments].

Six segments within the subunit beta-A of the follicular inhibin have been synthesized by an improved solid phase procedure on p-methyl-benzhydrylamine (1% divinylbenzene) resin. The courses of the syntheses were monitored by quantitative ninhydrin assays and amino acid analyses. Following the cleavage by HF-p-cresol (9:1 V/V), the peptides were extracted with anhydrous trifluoroacetic acid containing 1% dithiothreitol and precipitated with dry ethyl ether. The purification was achieved uniquely by reverse phase HPLC and final products were characterized by several TLC systems, analytical HPLC and amino acid analyses. Pituitary cell culture bioassays were performed to ascertain their biological activities. However, among these synthetic peptides, the small peptides Ib-beta A (37-39)NH2(I), Ib-beta A(34-39)NH2(II), and Ib-beta A(30-39)NH2(III) showed no significant suppression on the LHRH-induced FSH secretion; the large peptides Ib-beta A(23-39)NH2(IV), Ib-beta A(16-39)NH2(V), and Ib-beta A(14-39)NH2(VI) lack adequate solubility in neutral media, and other methods are to be sought to test their bioactivities.

[An experimental study on circulation changes of the left gastric vessels in schistosomiasis cirrhosis].

An experimental study on circulating changes of left gastric vessels in schistosomiasis was done on animal models. The result favoured the theory of A-V shunt and local hyperdynamic status. It is important for not only understanding the pathogenesis of the disease but also for selecting the operative procedures. According to this theory, the coronary-caval shunt is a procedure of choice for some cases.