Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats

Aim:

Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides.

Methods:

Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro.

Results:

A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001–2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2–1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability.

Conclusion:

Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.     

High rate of Hepatitis B virus infection among hairdressers in Ibadan,Nigeria

Hepatitis B virus (HBV) infection is a major public health problem for over two billion people infected globally. Occupationally exposed persons are at high risk of HBV infection and, apart from medical personnel, there is dearth of information concerning the prevalence and awareness of HBV among this population in Nigeria. This study was designed to determine the levels of HBV awareness and prevalence of HBV infection among hairdressers in Ibadan, Nigeria. Hairdressers and teachers (unmatched controls) in four local government areas in Ibadan were tested for HBV infection using ELISA technique. Dried blood spot (DBS) samples were collected from 171 participants. DBS elutes from the samples were tested for HBV surface antigen (HBsAg). The rate of HBV infection was higher (p = 0.005) among the hairdressers (13.0%) than teachers (4.8%). However, teachers were better informed about HBV (38%) compared to hairdressers (13%; p = 0.0001). Differences in HBV awareness and occupation type were found to be significant (P = 0.001). Hairdressers are at high risk of HBV infection and may constitute a major source of HBV spread among urban dwellers, especially in areas where awareness is low. Routine HBV screening and appropriate interventions for hairdressers are recommended to interrupt HBV transmission.     

Serotype of Nigerian rotavirus strains

Summary Three hundred and fourteen stool samples collected from children >5 years between December 1993 and August 1995 were analysed by PAGE, ELISA, PCR and Dot-blot hybridization technique for electropherotype and serotype distribution of rotavirus infection among Nigerian paediatric patients. 14.3% of the children were positive for rotavirus antigen. Children aged 6–9 months were most often infected, accounting for 35.6% of all positive samples. 91.1% of rotavirus-positive samples could be serotyped. Serotypes G2, G4 and G8 were not detected. Serotype G3 predominated (62.5%) in southern Nigeria, while mixed infection specificity was more widespread (63.6%) in northern Nigeria. The presence of some untypeable samples may indicate serotypes which the serotype-specific primers and cDNA probes used could not detect. Electropherotypes of 26 (57.7%) of the positive samples were determined. Two and 3 migration patterns were observed among the short and long-pattern electropherotypes, respectively. Implications for vaccine development and utilization in the country are discussed.     

Pregnancy outcome in the elderly primigravidae.

We assessed the effect of advancing maternal age ( 35 years) on the outcome of pregnancy in first births among 50 elderly primigravidae compared with a control group of 50 younger primigravidae (20-29 years) at the University College Hospital Ibadan from 1 January 1988 to 31 December 1992. Most of the elderly primigravidae were professionals and the majority of them (68%) had involuntary infertility. Frequent hospital admissions, preterm delivery, low birth weights and very high caesarean section rates were the major problems highlighted in the elderly primigravidae, while anaemia was more frequent in the younger primigravidae. Unnecessary caesarean sections on the excuse of 'precious' baby in the elderly primigravidae should be discouraged bearing in mind its medico-social implications. It is concluded that although the elderly primigravidae may have higher rates of complications of pregnancy, delivery and neonatal deaths their overall risk of referral to special care baby unit is not appreciably increased.     

Etiologic agents and outcome determinants of community-acquired pneumonia in urban children: a hospital-based study

Etiologic clues and prognostic indicators of community-acquired pneumonia (CAP) were sought in a 30-month study of under-5 admissions for acute lower respiratory infections (ALRIs). Investigative tools included blood culture, hemogram, immunofluorescence and serology. Associations of variables were tested using standard statistical tools. Of 419 ALRI, 323 (77%) had pneumonia, 234 (72.4%) bronchopneumonia, 66 (20.4%) lobar pneumonia and 23 (7.1%) both. More than 70% had poor parental socioeconomic parameters, 56.8% were overtly malnourished, 37.8% lived in overcrowded homes and 16.7% had been potentially exposed to wood smoke. Despite preconsultation antimicrobial use in 35.6%, 59 (28.8%) of 205 blood cultures proved positive; Staphylococcus aureus accounted for 22 (37.3%), Klebsiella species nine (15.3%) and Streptococcus pneumoniae three (5.1%). Ninety-two viruses were identified in 61 (50%) of 122 analyses. Respiratory syncytial virus (RSV) accounted for 28 (30.4%), parainfluenza virus type 3 (PIV-3) for 18 (19.5%) and influenza type-A (flu-A) 16 (17.3%). Twenty (16.4%) had > or = 2 viruses, while 40% of bacteremic cases with positive viral identification(s) had PIV-3. Pathogen detection was neither associated with hematologic parameters nor the final respiratory diagnosis. There were 35 (10.8%) deaths. Mortality was associated with maternal illiteracy (p = 0.045), wood smoke exposure (p = 0.006), preconsultation antimicrobial use (p = 0.04), malnutrition (p = 0.0003), bacteremia (p = 0.006) and polymorphonuclear leucocytosis (p = 0.023/0.013). RSV, PIV-3, flu-A, S. aureus and Klebsiella species constitute the major pathogens of pediatric CAP in urban Nigeria, while malnutrition, wood smoke exposure and bacteremia are strong risk factors of mortality. The poor prognostic import of antimicrobial abuse, vis-a-vis the apparent selection of necrotizing pathogens, are compelling indications for a reappraisal of current regional antimicrobial policies and exploring newer frontiers of disease control, including vaccine prevention.     

Isolation and characterization of a new subtype A variant of human immunodeficiency virus type I from Nigeria

We have isolated a new variant of HIV‐1 from Nigeria, Africa. The virus was recovered from the peripheral blood mononuclear cells (PBMCs) of an apparently healthy 23‐year‐old male from Ibadan, Nigeria. The in vitro studies indicated that the virus was highly cytopathic and replicated well in normal PBMCs, established T‐cell lines and the monocytic cell line U937. The highest replicative titre of the virus was obtained in freshly isolated primary macrophage/monocyte cells which also showed the least cytopathology. Most other cultures showed single‐cell cytolysis and giant cells, and syncytia were not induced in the HTLV‐1 infected MT‐2 cells. Since no HIV strain has been isolated from Nigeria, we obtained cDNA clones containing the env gene, to further characterize the Nigerian virus. Based on the DNA sequence analysis of 14 clones containing the coding region for its gp 120 protein, the Nigerian HIV isolate has been classified as HIV‐1 subtype A. Only one subtype A virus from Rwanda has been characterized and this virus has not been shown to exhibit extreme cytopathicity in various cell types as was observed with the Nigerian strain. Further, the ability of this virus to grow well in lymphocytes, monocytes and macrophages and to exhibit cytopathicity without causing syncytia are uncommon properties distinguishing the Nigerian virus from other HIV‐1 strains. Since most macrophage‐tropic viruses have been associated with 'neurotropism', the isolation of an HIV‐1 strain from the blood of an individual with no known neurological disorder indicates that this rapidly replicating cytopathic virus, with a broad host range, may play an important role in the pathogenesis of HIV disease. This represents the first report of an HIV‐1 isolate from Nigeria.     

Detection of HIV antigen and cDNA among antibody-negative blood samples in Nigeria

In developing countries as many as 50% of patients for whom a transfusion is indicated are at risk of dying immediately if transfusion is withheld. It is therefore important that blood transfusion is made as safe as possible. This study was designed to assess the safety of blood transfusion in two large blood banks in Ibadan, Nigeria. Aliquots of 250 samples already screened and passed as negative for HIV-1 and -2 were collected from each of the blood banks. Samples were tested for the presence of HIV-1 antigen (ELAVIA Ag I) and the antigen-positive samples tested for the presence of specific HIV-1 antibodies by Western blot (BioRad, France). All antigen-positive samples were also subjected to PCR. HIV-1 antigen was detected in 6 (1.2%) of the 500 samples, of which 4 (0.8%) and 3 (0.6%) were Western blot-indeterminate and PCR-positive, respectively. Transfusion of HIV-contaminated blood may be contributing significantly to the spread of the virus in Nigeria. There is therefore an urgent need for an organized blood-banking system with facilities for more sensitive assays for the detection of HIV in blood to prevent transmission through transfusion.