bluuebunny/crossref_metadata_2025 huggingface dataset:
The evaluation of the role of CCK in the opioid modulation of the motility of the gastrointestinal tract in sheep
Authors: Kania  , Brikas  , BuÉno  , Fioramonti  , Zaremba‐Rutkowska
Published: March 2003

The participation of central cholecystokinin‐8 (CCK‐8) receptors in the modulatory effect of D‐Ala2, N‐Me‐Phe4, Gly5‐ol enkephalin (DAGO), a selective μ–opioid receptor agonist, on the spike burst activity of the gastrointestinal tract (rumen, reticulum, antrum, duodenum, colon and caecum) in sheep was investigated. DAGO was infused intracerebroventricularly (i.c.v.) at doses of 0.1–1 μg/kg body weight (BW).

 It was shown that DAGO significantly inhibited myoelectrical activity of the wall of the forestomachs, abomasum and colon but stimulated this activity in the duodenum (rate of myoelectrical migrant complex‐MMC). The effects of DAGO were prevented by CCK‐8 antagonists (L‐364.718 and L‐365.260) previously infused at doses of 5–20 μg/kg BW.

 The results of this present study indicate that central receptors of CCK‐8 participated in the modulatory action of an opioid on myoelectrical activity of the gastrointestinal tract in sheep. Furthermore, this result suggests that CCK‐8 is released in response to μ‐receptor stimulation, because CCK‐8 antagonists (L 364.718 and L 365.260) prevented the modulatory action of DAGO on the gastrointestinal motility in sheep.
Haemodynamic effects of ATP in dogs during hypoxia‐induced pulmonary hypertension
Authors: Driessen B. , Haskins S.C. , Pascoe P.J. , Tripp L.D. , Reitan J.A.
Published: March 2003

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03–3.0 μmol/kg/min ≈ 0.02–1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose‐dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P < 0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose‐dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.
Plasma angiotensin converting enzyme activity and pharmacokinetics of benazepril and benazeprilat in cats after single and repeated oral administration of benazepril.HCl
Authors: King  , Humbert‐Droz  , Maurer
Published: March 2003

The plasma pharmacokinetics of benazepril and its active metabolite, benazeprilat, were determined in cats after oral administration of benazepril.HCl at dosages of 0.25, 0.5 and 1.0 mg/kg as a single dose (n = 5 per group) and after once daily application for 8 days (n = 6 per group). Pharmacodynamics were assessed by measurement of plasma angiotensin converting enzyme (ACE) activity.

After single administration of benazepril.HCl, maximum benazepril concentrations were recorded at the first sample (2 h) and declined relatively rapidly with an elimination half life (t½) of 1.4 h. Highest benazeprilat concentrations were recorded at the first sample (2 h) in most cats and declined biphasically with half lives of each phase of 2.4 and 27.7 h. With repeated administration, plasma benazeprilat concentrations accumulated slightly with accumulation ratios (R) of 1.46, 1.36 and 1.24 for the 0.25, 0.5 and 1.0 mg/kg dosages of benazepril.HCl, respectively (median value of 1.36 for all dosages).

All three dosages of benazepril.HCl caused marked inhibition of plasma ACE activity in all cats. The maximum effect (Emax, % inhibition of ACE as compared to baseline) was  98% after single and 100% with repeated administration. The duration of action of benazepril.HCl was long, with > 87% (single) and > 90% (repeat) inhibition of plasma ACE persisting 24 h after dosing.

Benazepril.HCl was well tolerated in all animals. Dosages of 0.25–1.0 mg/kg benazepril.HCl once daily are recommended for clinical testing in cats.
Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs
Authors: Kuusela  , Raekallio  , Anttila  , Falck  , Mölsä  , Vainio
Published: March 2003

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti‐omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 μg/kg), DEX (20 and 10 μg/kg), LEVO (20 and 10 μg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (± SD) plasma levels of 18.5 ± 4.7 ng/mL for MED40, 14.0 ± 4.5 ng/mL for DEX20, and 5.5 ± 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio‐vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 ± 0.69 L/h/kg for LEVO20 and 3.52 ± 1.03 for LEVO10) than of the other drugs (1.26 ± 0.44 L/h/kg for MED40, 1.24 ± 0.48 for DEX20, and 0.97 ± 0.33 for DEX10).
The effect of raloxifene on coronary arteries in aged ovariectomized ewes
Authors: Gaynor J. S. , Monnet E. , Selzman C. , Parker D. , Kaufman L. , Bryant H. U. , Mallinckrodt C. , Wrigley R. , Whitehill T. , Turner A. S.
Published: March 2003

Background – Ovariectomized sheep are a useful model of postmenopausal osteoporosis and other postmenopausal conditions. Estrogen may have a protective effect on the coronary arteries in postmenopausal women. The effects of raloxifene, a selective estrogen receptor modulator, on coronary arteries in aged ovariectomized ewes was investigated.

Methods and Results – Forty eight aged ewes were randomly assigned to undergo sham surgery (Sham, n=7), ovariectomy (OVX, n=10), ovariectomy with estradiol supplementation (OVXE, n=8), ovariectomy with raloxifene supplementation, 0.02 mg/kg per day (RAL1, n=10), or ovariectomy with raloxifene supplementation, 0.10 mg/kg per day (RAL2, n=13). Contrast coronary angiography was performed 6 months after intervention. Diameters of the right main and left anterior descending coronary arteries in the RAL1, RAL2 and Sham groups were not different from each other, but were significantly greater than the OVX and OVXE groups. Intracoronary nitroglycerin did not affect the relationships of the diameters in any group. There were no differences in vascular remodeling between the groups.

Conclusions – The results indicate that raloxifene in this sheep model allows greater dilation of coronary arteries than estrogen. Raloxifene may provide a significant protective functional effect on coronary arteries in postmenopausal heart disease.
Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions
Authors: Craven J. , Bjørn H. , Hennessy D. , Friis C. , Nansen P.
Published: March 2003

Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long protective period after administration because of their extensive distribution into fat. This study examined whether the body composition of the animal at the time of treatment had any influence on the pharmacokinetics of two MLs, moxidectin (MOX) and ivermectin (IVM). ‘Fat’ and ‘lean’ lines of pigs were established using two different diets, with weekly determination of liveweight and backfat thickness confirming the difference in body condition between the groups. Blood samples were taken at regular intervals following i.v. injection of IVM or MOX at a dose of 300 μg/kg and the plasma was analysed using fluorescence high performance liquid chromatography (HPLC) to determine the concentration of IVM or MOX in the samples. Regardless of body composition IVM and MOX kinetics were very different with MOX having a greater apparent volume of distribution, longer distribution and elimination half‐lives and a slower clearance rate than IVM, which led to MOX being detectable in plasma for >40 days compared with only 8–10 days for IVM. Altering body composition had no detectable influence on the kinetic disposition of IVM in this study. In contrast, although there was no difference in AUC or the volume of distribution, MOX was distributed within and eliminated from the lean animals more rapidly than from the fat animals.
Measurement of ketoprofen in horse urine using gas chromatography‐mass spectrometry
Authors: Kim J. Y. , Kim S. J. , Paeng K.‐J. , Chung B. C.
Published: March 2003

A gas chromatographic‐mass spectrometric (GC‐MS) method for the determination of ketoprofen, a non‐steroidal anti‐inflammatory drug (NSAID), in horse urine by selected ion monitoring (SIM) mode is described. Urine samples (2 mL) were extracted by liquid–liquid extraction with diethyl ether. The residues were then evaporated, derivatized and injected into the GC‐MS system. Validation of the GC‐MS method in the SIM mode using flurbiprofen as the internal standard (IS) included linearity studies (10–10 000 ng/mL), recovery (95%) and limit of quantitation (LOQ) (10 ng/mL). The response was linear, with a correlation coefficient (0.9998) for ketoprofen. When applied to horse urine samples, the present method allowed detection of ketoprofen up to 16 days in FULL SCAN mode after a topical application of 1.1 g of ketoprofen in a gel formulation.
Effects of anti‐arthritic drugs on proteoglycan synthesis by equine cartilage
Authors: Frean S. P. , Cambridge H. , Lees P.
Published: March 2003

Effects of anti‐arthritic drugs on proteoglycan synthesis by equine cartilage.J. vet. Pharmacol. Therap.25,289–298.

The concentration–effect relationships of phenylbutazone, indomethacin, betamethasone, pentosan polysulphate (PPS) and polysulphated glycosaminoglycan (PSGAG), on proteoglycan synthesis by equine cultured chondrocytes grown in monolayers, and articular cartilage explants were measured. The effect of PSGAG on interleukin‐1βinduced suppression of proteogycan synthesis was also investigated. Proteoglycan synthesis was measured by scintillation assay of radiolabelled sulphate (35SO4) incorporation. Polysulphated glycosaminoglycan and PPS stimulated proteoglycan synthesis in chondrocyte monolayers in a concentration‐related manner with maximal effects being achieved at a concentration of 10 μg/mL. Polysulphated glycosaminoglycan reversed the concentration‐related suppression of proteoglycan synthesis induced by interleukin‐1β. Neither PSGAG nor PPS exerted significant effects on radiolabel incorporation in cartilage explants. Betamethasone suppressed proteoglycan synthesis by both chondrocytes and explants at high concentrations (0.1–100 μg/mL), but the effect was not concentration‐related. At low concentrations (0.001–0.05 μg/mL) betamethasone neither increased nor decreased proteoglycan synthesis. Phenylbutazone and indomethacin increased radiolabel incorporation in chondrocyte cultures but not in cartilage explants at low (0.1, 1 and 10 μg/mL), but not at high (20 and 100 μg/mL) concentrations. These findings may be relevant to the clinical use of these drugs in the treatment of equine disease.
Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits
Authors: Escudero E. , Vicente M. S. , Serrano J. M. , Cárceles C. M.
Published: March 2003

. Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits.J. vet. Pharmacol. Therap.25,259–264.

The pharmacokinetics of a 2:1 ampicillin–sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration–time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two‐compartment model after intravenous administration and a one‐compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 ± 0.09 and 0.45 ± 0.05 L/kg, respectively, and the total body clearances were 0.65 ± 0.04 and 0.42 ± 0.05 L/kg h, respectively. The elimination half‐lives of ampicillin after intravenous and intramuscular administration were 0.64 ± 0.11 and 0.63 ± 0.16 h, respectively, whereas for sulbactam the half‐lives were 0.74 ± 0.12 and 0.77 ± 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 ± 10.08% for ampicillin and 83.20 ± 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 ± 0.09 and 0.34 ± 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 ± 3.64 mg/L of ampicillin and 8.42 ± 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.
Relationship between biochemical and virological responses to interferon therapy in chronic hepatitis C infection
Authors: Pockros P. J. , Tong M. , Lee W. M. , Van Leeuwen D. J. , Keeffe E. B. , Bala K. , Killenberg P. G. , Foust R. T. , Rosenblate H. J. , Payne K. M. , Fromm H. , Lesesne H. R. , Black M. , Group The Consensus Interferon Study
Published: March 2003

We have investigated the relationship between serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA in the assessment of responses to interferon (IFN) therapy in chronic HCV infection. Data from 704 patients with HCV infection who were randomized to receive consensus IFN‐α (CIFN) 3μg (n=232 patients) or 9μg (n=232 patients), or IFN‐α2b 3 million units (MU) (n=240 patients), were used for these analyses. All patients were treated three times weekly for 24 weeks and then were observed for a further 24 weeks. Hepatitis C viral RNA (HCV RNA) was determined by quantitative reverse transcriptase–polymerase chain reaction (RT–PCR) with a lower limit of detection of 100 copiesml–1. Of patients with normal serum ALT concentrations, 53% (120/225) had undetectable HCV RNA at the end‐of‐treatment period and 47% (51/109) had undetectable HCV RNA at the end of the post‐treatment observation period. In contrast, of the patients with undetectable HCV RNA, 75% (120/161) and 84% (51/61) had normal serum ALT activities at the end‐of‐treatment and post‐treatment observations periods, respectively. The majority of patients with undetectable HCV RNA had normal ALT values. In contrast, only half of the patients with normal ALT values were negative for HCV. End‐of‐treatment HCV RNA response also better predicted sustained virological response than did end‐of‐treatment ALT response.
Significance of antibodies to the recombinant E2 protein of hepatitis G virus in haemodialysis patients
Authors: Schulte‐Frohlinde E. , Schmolke S. , Reindl W. , Schätzle G. , Scherf J. , Kopp K. F. , Classen M. , Schlüter V.
Published: March 2003

Patients on maintenance haemodialysis represent a high‐risk group for parenterally transmitted viral infections, such as hepatitis B, C and G. In addition to hepatitis G virus (HGV) (GBV‐C) RNA, analysed in previous studies, we characterized the seroprevalence rates of antibodies to the putative E2 protein (anti‐E2) of HGV in a German cohort of patients on maintenance dialysis (n = 72) in comparison to healthy blood donors (n = 100). The presence of anti‐E2 and/or HGV RNA as indicators of present or past HGV infection could be demonstrated in 34.7% of patients and in 16% of the blood donors (P < 0.01). The infection rates with HGV seem to increase only during the first 6 years of haemodialysis. The simultaneous presence of viraemia and anti‐E2 was found very rarely in patients and controls. Therefore, the emergence of anti‐E2 indicates clearance of HGV viraemia. In conclusion, patients on haemodialysis are at high risk of acquiring HGV infection, but a chronic carrier state with viraemia is rare. The risk of infection is not strictly correlated with the duration of dialysis.
Hepatitis E virus: can it be transmitted parenterally?
Authors: Arankalle V. A. , Chobe L. P.
Published: March 2003

Of 200 voluntary blood donors screened for hepatitis E virus (HEV) RNA, employing the reverse transcription–polymerase chain reaction (RT–PCR), three were found to be positive (1.5%). None of the HEV RNA‐positive blood donors had any symptoms at the time of blood donation or during subsequent follow‐up. One donor was positive for immunoglobulinM (IgM) antibodies to HEV, with a raised serum alanine aminotransferase (ALT) level, whereas the other two donors were negative for both immunoglobulinG (IgG) and IgM antibodies to HEV. Follow‐up blood samples collected 2–5months later from HEV RNA‐positive blood donors demonstrated the presence of IgG anti‐HEV antibodies. Overall seroprevalence of IgG anti‐HEV was 18.6%. Retrospective studies on samples collected from commercial blood donors and haemophiliacs revealed IgG anti‐HEV positivity to be 24.6% (46/191) and 24.4% (22/90) and statistically not different (P>0.1) from the prevalence among voluntary blood donors and an age‐matched normal population, respectively. However, a highly significant proportion of the paid plasma donors, with a high prevalence of IgG antibodies to human immunodeficiency virus and hepatitis C virus, were positive for IgG antibodies to HEV (54/71, 76%, P<0.001), indicating a possible role of blood‐derived HEV in the transmission of the virus among plasma donors. These results demonstrate the possible risk of transfusion‐associated hepatitis E in hyperendemic areas.
Long‐term administration of interferon‐α in non‐responder patients with chronic hepatitis C: follow‐up of liver fibrosis over 5 years
Authors: Guerret S. , Desmoulière A. , Chossegros P. , Costa A. M. A. , Badid C. , Trépo C. , Grimaud J. A. , Chevallier M.
Published: March 2003

In chronic hepatitis C, previous data have shown that short‐term treatment with interferon‐α (IFN‐α) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non‐responder patients, the long‐term effect of IFN‐α on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non‐responder patients with chronic hepatitis C retreated with successive courses of IFN‐α. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN‐α treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN‐α therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow‐up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow‐up period in all patients (P = 0.045). Long‐term treatment with IFN‐α is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.
Patients co‐infected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA
Authors: Bonacini M. , Govindarajan S. , Blatt L. M. , Schmid P. , Conrad A. , Lindsay K. L.
Published: March 2003

Serum and liver hepatitis C virus (HCV) RNA levels in patients with hepatitis C have previously been quantified using different techniques. In this work, we used an automated, multicycle, polymerase chain reaction (PCR)‐based technique to quantify HCV RNA in 1–2 mm of frozen liver tissue, and in serum, from 70 patients with antibodies to HCV (anti‐HCV), with and without human immunodeficiency virus (HIV) co‐infection. Stored liver tissue and sera collected at the time of liver biopsy were used for measurement of HCV RNA. Forty‐eight HCV patients and 22 HIV/HCV co‐infected patients were studied. Co‐infected patients had significantly higher median serum and liver HCV RNA (6.7 log copies ml–1 serum and 2.90 log copies μg–1 liver nucleic acids) than patients with HCV alone (6.2 log copies ml–1 serum and 2.19 log copies μg–1 liver nucleic acids). There was only a weak correlation between serum and liver HCV RNA (r = 0.43). There was no correlation between liver and serum HCV RNA and host factors such as duration of disease, CD4 counts, alanine aminotransferase levels or histological score. There was no correlation with HCV genotype. Co‐infected patients were more likely to harbour HCV genotype 1 (85%) when compared to patients with HCV alone (58%). An identical genotype was found in liver and serum in 89% of those tested; in 11%, a mixed genotype was present in serum. Patients with HCV genotypes 1 and non‐1 had similar histological scores. Hence, an automated PCR‐based technique is useful for measuring both liver and serum HCV RNA. Serum HCV genotypes closely paralleled those found in liver tissue. HIV co‐infection was associated with higher serum, as well as intrahepatic, HCV RNA levels, by mechanisms not directly related to CD4 counts. The lack of correlation between liver HCV RNA and histology suggests that HCV is not directly cytopathic.
A short induction regimen of interferon‐α is not effective for treatment of relapse in chronic hepatitis C: a randomized trial
Authors: Poynard T. , Daurat V. , Chevret S. , Moussalli J. , Degos F. , Bailly F. , Borotto E. , Buffet C. , Bartolomei‐Portal I. , Richardet J. P. , Riachi G. , Calmus Y. , Bréchot C. , Vidaud M. , Olivi M. , Bedossa P. , Riffaud P. Chaumet , Chastang C.
Published: March 2003

The aim of this work was to assess the effect of a high‐dose (10 million units, MU) short‐duration (14 weeks) interferon‐α2b (IFN‐α2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty‐eight non‐cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high‐dose, short‐duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high‐dose, short‐duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72‐week follow‐up, in the high‐dose, short‐duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high‐dose, short‐duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high‐dose, short‐duration treatment with IFN‐α has no advantage when compared to a 6‐month treatment with 3 MU IFN t.i.w.
Serum levels of hepatitis C virus RNA predict non‐response to interferon therapy: comparison of two commercial assays
Authors: Soffredini R. , Rumi M. G. , Del Ninno E. , Parravicini M. L. , Russo A. , Colombo M.
Published: March 2003

We compared two commercial assays for quantification of serum hepatitis C virus (HCV) RNA to investigate whether pretreatment levels of serum HCV RNA could predict the outcome of interferon (IFN) therapy. The Amplicor HCV Monitor test is based on a single, combined reverse transcription and amplification reaction carried out by the Tth DNA polymerase using specific primers for the 5′ untranslated
(UTR) region. The Quantiplex HCV RNA 2.0 assay is based on specific hybridization
of viral RNA by synthetic oligonucleotides complementary to the 5′‐UTR and
core regions of the genome, allowing equal quantification of the six major genotypes.
Receiver‐operating characteristic (ROC) analysis was employed to identify the best
cut‐off value (predicting patients who were non‐responsive to treatment) with corresponding
sensitivity and specificity values. Logistic regression analysis was performed using
these cut‐off values. We studied 133 consecutive patients with chronic hepatitis
C enrolled in a prospective trial of IFN‐α therapy (18 of whom were sustained
complete responders). The median viraemia of the 18 sustained responders was 5322
copies ml–1 by the Monitor test and less than 0.2million equivalents
ml–1 (MEq ml–1) by the Quantiplex assay; for
the 115 non‐responders/relapsers, the median viraemia was 83125 copies ml–1
and 1.128 MEq ml–1 for the Monitor test and Quantiplex assay, respectively.
Spearman’s rank test gave a correlation of 0.63 between assays. The best predicting
cut‐off values were 22134 copies ml–1 for the Monitor test and
0.330 MEq ml–1 for the Quantiplex assay; their respective sensitivities
and specificities were 72% and 75% for Monitor and 67% and
83% for Quantiplex. By logistic regression analysis, the age and gender‐adjusted
odds ratios of high vs low HCV RNA levels, defining the risk of non‐response, were 10.6 (CI 3.1–35.7) for Monitor and 14.3 (CI 4.3–47.3) for Quantiplex. The two assays had comparable sensitivity for serum HCV RNA but they identified different predictive cut‐offs for non‐response to therapy.
Detection and viral nucleotide sequence analysis of transfusion‐transmitted virus infection in acute fulminant and non‐fulminant hepatitis
Authors: Huang  , Wu  , Chiang  , Chan  , Huo  , Huang  , Hwang  , Chang  , Lee
Published: March 2003

The impact of transfusion‐transmitted virus (TTV) infection on acute fulminant and non‐fulminant hepatitis is unclear. In this study, serum samples from 164 patients with acute hepatitis of various aetiologies, from 34 asymptomatic hepatitis B virus carriers and from 202 healthy adults were tested for TTV DNA by the semiconserved nested polymerase chain reaction. TTV viraemia was prevalent in patients with acute hepatitis C, in patients with acute hepatitis D virus superinfection and in patients with non‐A–E hepatitis (27–30%) but the incidence was not significantly different from that of healthy controls (31 of 202, 15.3%). There were no significant differences in gender, age, presence of hepatitis G virus, the occurrence of fulminant hepatitis, or in serum albumin, bilirubin or alanine aminotransferase levels (9/30 vs 35/134) between patients with or without TTV viraemia. Seven of the nine TTV‐positive patients with fulminant hepatitis were co‐infected with hepatitis C, D or E. TTV clones from 18 subjects, with or without fulminant hepatitis, were sequenced and analysed phylogenetically. Eleven (61.1%) belonged to TTV group 1, six (33.3%) to TTV group 2 and one to TTV group 3. No particular strain of TTV was associated with fulminant hepatitis. In summary, in Taiwan, TTV is prevalent in the general population as well as in patients with liver diseases. TTV plays an insignificant role in acute fulminant and non‐fulminant hepatitis. Its influence on outcome requires a longitudinal study.
Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis B
Authors: Lindh  , Horal  , Dhillon  , Norkrans
Published: March 2003

The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying whether ‘healthy carriers’ can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen‐negative (HBeAg−) patients, the majority with mild liver disease, log HBV DNA levels showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml−1, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl ≥ 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg− patients with HBV DNA > 107, > 2 × 105 and < 104 copies ml−1, respectively. In severe HBeAg− hepatitis, patients with precore wild‐type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg‐positive (HBeAg+) patients, no correlation between HBV DNA level and liver damage was seen. Ninety‐six per cent of HBeAg− patients with ALTi < 0.5 had HAIinfl ≤ 3. In HBeAg− carriers with ALTi 0.5–1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 105 copies ml−1vs < 2 × 105 copies ml−1, was 14.7. In conclusion, in HBeAg− carriers, HBV DNA < 104 copies ml−1 or ALTi < 0.5 indicates mild inflammation, while > 2 × 105 copies ml−1 of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia.
Retinal vein thrombosis associated with chronic hepatitis C: a case series and review of the literature
Authors: Nadir A. , Amin A. , Chalisa N. , Van Thiel D. H.
Published: March 2003

The role of procoagulant autoantibodies in hepatitis C virus (HCV) infection is unclear. Three individuals with HCV infection and a unique genetic hypercoagulable state developed retinal vein thrombosis (RVT) in association with interferon‐α (IFN‐α) therapy. It is probable that a combination of active HCV infection in a genetically susceptible individual receiving IFN‐α accounted for the observed RVT.
Haemophilic patients with hepatitis C have higher viral load compared to other well‐defined patient groups
Authors: Krarup H. B. , Møller J. M. , Christensen P. B. , Fuglsang T. , Ingerslev J. , Arnfred T. , Madsen P. H.
Published: March 2003

Comparison of hepatitis C viral load between different patient populations has been hampered by the use of different technology in individual studies. We had the impression that haemophilic (HAEM) patients had a higher serum load of hepatitis C virus (HCV) compared to other HCV‐infected patients. We therefore studied viral load and genotypes in active illicit drug users (IDU), HAEM patients and patients with post‐transfusion hepatitis (PTH). The study comprises 225 HCV‐RNA positive patients, 117 IDU, 60 HAEM patients and 48 PTH patients. All patients were anti‐HIV negative. HCV‐RNA was measured with a quantitative reverse transcription polymerase chain reaction (RT–PCR) method, HCV‐genotypes were determined with genotype specific primers in RT–PCR in 221 patients. Four patients could not be genotyped with our assay and were excluded. Overall viral load was higher in genotypes 1 and 2 compared to genotype 3, median values of HCV‐RNA were 1400 × 103 geq ml−1, 2700 × 103 geq ml−1 and 270 × 103 geq ml−1, respectively. HAEM patients had significantly higher viral load for both genotypes 1 and 3 compared to the IDU and PTH patients. In a multiple linear regression model HCV‐RNA viral load was independently associated with HAEM and genotype, but not to age, gender or disease duration. In conclusion, HAEM patients have higher viral load than IDU and PTH patients. The reason for this is unknown, but it may be due to host factors or mode of transmission with multiple inoculations.
Immunological response to interferon‐γ priming prior to interferon‐α treatment in refractory chronic hepatitis C in relation to viral clearance
Authors: Katayama K. , Kasahara A. , Sasaki Y. , Kashiwagi T. , Naito M. , Masuzawa M. , Katoh M. , Yoshihara H. , Kamada T. , Mukuda T. , Hijioka T. , Hori M. , Hayashi N.
Published: March 2003

The aim of this study was to clarify the immunological and virological responses to pre‐administration of interferon‐γ prior to initiation of interferon‐α treatment in patients with refractory chronic hepatitis C. Twenty‐two nonresponders to 6‐months of IFN‐α treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN‐γ (1 MIU/day) was administered daily for 14 days followed by natural IFN‐α (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL‐10, neopterin, BMG, sCD8, sCD4, IL‐6, IL‐12) were measured as were the levels of several cytokines (IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN‐α treatment, HCV‐RNA had become negative in six of 19 patients (end‐of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL‐10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN‐γ administration, and tended to return to the pretreatment level after the start of IFN‐α administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN‐γ prior to the initiation of IFN‐α treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.
Pilot study of interferon‐α and ribavirin treatment in patients with chronic hepatitis C and normal transaminase values
Authors: Lee Samuel S. , Sherman Morris
Published: March 2003

Combination interferon‐α (IFN‐α) and ribavirin treatment has become standard therapy for patients with chronic hepatitis C and elevated transaminase levels (> 1.5 × upper limit of normal). No previous study has specifically examined the efficacy of this treatment in patients with normal transaminase values. In this pilot study, we treated 19 patients, with normal or near‐normal ALT values on at least three occasions, and histologically mild disease, with induction IFN‐α2b, 5 mega units daily for 4 weeks, then 3 mega units thrice weekly for 44 week, plus concomitant ribavirin 1000 mg or 1200 mg daily for 48 weeks. Nine of the 19 (47%) showed sustained virological response, defined as undetectable HCV‐RNA at 24 weeks after the end of treatment. No ALT flares were observed in any patient. We conclude that combination induction IFN‐α and ribavirin therapy may be effective in patients with normal‐ALT, and appears not to induce flares of ALT activity. Controlled trials of this treatment in this subgroup of patients with hepatitis C are warranted.
Baleen whales: conservation issues and the status of the most endangered populations
Authors: Clapham Phillip J. , Young Sharon B. , Brownell Robert L.
Published: March 2003

Most species of baleen whales were subject to intensive overexploitation by commercial whaling in this and previous centuries, and many populations were reduced to small fractions of their original sizes. Here, we review the status of baleen whale stocks, with an emphasis on those that are known or thought to be critically endangered. Current data suggest that, of the various threats potentially affecting baleen whales, only entanglement in fishing gear and ship strikes may be significant at the population level, and then only in those populations which are already at critically low abundance. The impact of some problems (vessel harassment, and commercial or aboriginal whaling) is at present probably minor. For others (contaminants, habitat degradation, disease), existing data either indicate no immediate cause for concern, or are insufficient to permit an assessment. While the prospect for many baleen whales appears good, there are notable exceptions; populations that are of greatest concern are those suffering from low abundance and associated problems, including (in some cases) anthropogenic mortality. These include: all Northern Right Whales Eubalaena glacialis, Bowhead Whales Balaena mysticetus of the Okhotsk Sea and various eastern Arctic populations, western Gray Whales Eschrichtius robustus, and probably many Blue Whale Balaenoptera musculus populations. We review the status of these populations and, where known, the issues potentially affecting their recovery. Although Humpback Whales Megaptera novaeangliae and Southern Right Whales Eubalaena australis were also heavily exploited by whaling, existing data indicate strong recovery in most studied populations of these species.
Rainfall, ambient temperature, and Clethrionomys californicus capture frequency
Authors: Maguire Chris C.
Published: March 2003

Sixty Western Red‐backed Voles Clethrionomys californicus inhabiting an old‐growth mixed conifer forest in north‐western California (USA) were studied over 2 years to assess relationships among vole capture frequency, rainfall, and ambient temperature. Red‐backed Voles were encountered more often and recapture rates per vole doubled with the tripling of yearly rainfall. In addition, more voles were captured during wet months than dry months. Analysed over weekly intervals, captures were positively correlated with the amount of weekly rainfall, a greater proportion of the known vole population was encountered during wet weeks than dry weeks, and increased weekly rainfall resulted in an increased proportion of the vole population captured. Significant relationships were not found between daily rainfall and vole captures, but both minimum and maximum daily ambient temperatures were lower when voles were trapped. Vole captures increased with decreases in daily and weekly minimum and maximum ambient temperatures. Weekly rainfall in combination with minimum weekly temperatures accounted for the greatest explanation of variability in vole capture frequencies. These results document that rainfall and ambient temperature have an impact on Western Red‐backed Vole capture frequency; thus these weather variables should be addressed as covariates in analyses focused on capture data for this species.
Differential responses of mosquito sibling species Anopheles arabiensis and An. quadriannulatusto carbon dioxide, a man or a calf
Authors: DEKKER TEUN , TAKKEN WILLEM
Published: March 2003

Field studies on responses of two mosquito sibling species, Anopheles arabiensis Patton and An. quadriannulatus Theobald, to a man, a calf and different release rates of carbon dioxide (man, calf and cow equivalents) were conducted in north‐eastern South Africa. Various combinations of baits were compared in two‐choice tests, using two mosquito nets, placed 2.5 m apart and 10 cm off the ground. Mosquitoes attracted to the baits were able to enter the nets from below and were collected by means of a suction tube. In a two‐choice test between a man and CO2 (human equivalent, 250 ml/min), 81% of the An. quadriannulatus were caught with CO2. The reverse was seen for An. arabiensis, where only 20% of the total catch was caught with CO2 compared to man. High release rates of CO2 (cow equivalent, 800 ml/min) attracted significantly more An. quadriannulatus than the low release rate (250 ml/min), whereas no significant effect of the release rate of CO2 on the total catch of An. arabiensis was seen. In the latter species, up to 33% of the attraction of human emanation is attributable to carbon dioxide. Anopheles quadriannulatus was equally attracted to a calf and CO2 (calf equivalent, 180 ml/min). Catches of other mosquito species showed consistent differences between all treatments which appear to be associated with differences in host‐preference, suggesting that the importance of CO2 in host‐seeking behaviour of mosquitoes increases with the degree of zoophily.
Resistance management strategies in malaria vector mosquito control. Baseline data for a large‐scale field trial against Anopheles albimanus in Mexico
Authors: PENILLA PATRICIA R. , RODRÍGUEZ AMÉRICO D. , HEMINGWAY JANET , TORRES JOSÉ L. , ARREDONDO‐JIMÉNEZ JUAN I. , RODRÍGUEZ MARIO H.
Published: March 2003

Abstract.A high level of DDT resistance and low levels of resistance to organophosphorus, carbamate and pyrethroid insecticides were detected by discriminating dose assays in field populations of Anopheles albimanus in Chiapas, southern Mexico, prior to a large‐scale resistance management project described by Hemingway et al. (1997) . Biochemical assays showed that the DDT resistance was caused by elevated levels of glutathione S‐transferase (GST) activity leading to increased rates of metabolism of DDT to DDE. The numbers of individuals with elevated GST and DDT resistance were well correlated, suggesting that this is the only major DDT resistance mechanism in this population.

The carbamate resistance in this population is conferred by an altered acetylcholinesterase (AChE) ‐based resistance mechanism. The level of resistance observed in the bioassays correlates with the frequency of individuals homozygous for the altered AChE allele. This suggests that the level of resistance conferred by this mechanism in its heterozygous state is below the level of detection by the WHO carbamate discriminating dosage bioassay.

The low levels of organophosphate (OP) and pyrethroid resistance could be conferred by either the elevated esterase or monooxygenase enzymes. The esterases were elevated only with the substrate pNPA, and are unlikely to be causing broad spectrum OP resistance. The altered AChE mechanism may also be contributing to the OP but not the pyrethroid resistance.

Significant differences in resistance gene frequencies were obtained from the F1 mosquitoes resulting from adults obtained by different collection methods. This may be caused by different insecticide selection pressures on the insects immediately prior to collection, or may be an indication that the indoor‐ and outdoor‐resting A. albimanus collections are not from a randomly mating single population. The underlying genetic variability of the populations is currently being investigated by molecular methods.
Identification of five species of the Anopheles dirus complex from Thailand, using allele‐specific polymerase chain reaction
Authors: Walton C. , Handley J. M. , Kuvangkadilok C. , Collins F. H. , Harbach R. E. , Baimai V. , Butlin R. K.
Published: March 2003

The Anopheles dirus complex of mosquitoes contains some of the most important vectors of malaria in Southeast Asia. To distinguish five species of the complex that occur in Thailand, a method using the polymerase chain reaction (PCR) was developed. The method utilizes allele‐specific amplification to detect fixed differences between the species in the DNA sequence of the ribosomal DNA internal transcribed spacer 2. Primers were designed to amplify fragments of diagnostic length from the DNA of the different species. The method was tested on 179 mosquitoes of the An. dirus complex from many parts of Thailand and shown to be effective. Every specimen was unambiguously identified as species A, B, C, D or F (i.e. An. dirus s.s. species B, C, D or An. nemophilous, respectively) by the PCR method, with confirmation of 58/61 identifications from polytene chromosome characteristics. For the other three specimens (3/44 from Kanchanaburi 5 locality), there was disagreement between the PCR and chromosomal methods of species identification (probably due to errors in the chromosomal identifications). Primers can be combined in a single PCR reaction providing a rapid, sensitive and straightforward method of species identification. Only small quantities of DNA are required, leaving most of the mosquito to be used for other analyses.
Behavioural mode of action of deet: inhibition of lactic acid attraction
Authors: Dogan E. B. , Ayres J. W. , Rossignol P. A.
Published: March 2003

Using the mosquito Aedes aegypti in a novel olfactometer that measures movement towards and away from a stimulus, we could not confirm that ‘deet’ is a repellent of mosquitoes. In the absence of a host, deet was an attractant and in the presence of a host, it was an inhibitor of attraction. This inhibition occurred in the gaseous phase and was therefore not the result of the physical properties of deet. We determined that
l‐lactic acid, a component of human sweat that is an attractant to mosquitoes, is the target of this inhibition, implying that lactic acid may be a bottleneck in the behavioural cascade preceding blood‐sucking.
Morphology of a newly discovered sensory array on the mouthhooks of Gasterophilus larvae
Authors: Cogley T. P.
Published: March 2003

The distal mouthhooks of Gasterophilus intestinalis (DeGeer) (Diptera: Gasterophilidae) and G. nasalis (Linnaeus) (Diptera: Gasterophilidae) larvae were studied with scanning electron microscopy to determine the morphology of a previously unknown sensory array. The design of the 3rd stage G. intestinalis sensory array was used as the model for comparison to the 2nd stage of this species and the 2nd and 3rd stadia of G. nasalis. Some components forming the sensory array of the 3rd stage G. intestinalis mouthhook were found in 3rd stage G. nasalis. A major difference between these species was the replacement of shallow pits with sensilla‐laden troughs in G. nasalis. Second‐stage G. intestinalis has a distal mouthhook that varies considerably from the model type, lacking shallow pits and associated peg‐like sensilla. By contrast, the sensory array of the 2nd stage G. nasalis larva is the most elaborate yet encountered, with extensive sensilla and troughs. The existence of other types of sensilla on the mouthhook is proposed, as well as a sensory role for the unsculptured surface. Possible uses of the sensory array by the parasite are discussed.