Anti-inflammatory and analgesic properties of the stem bark extracts of Erythrophleum suaveolens (Caesalpiniaceae), Guillemin & Perrottet

The MeOH stem bark extract of Erythrophleum suaveolens dissolved in water and shaken up with ethylacetate (EtOAc) and fractionated on a polyamide column with methanol as eluent produced five principal fractions. These fractions were designated as fraction A (74.8 mg yield and rich in alkaloids), fraction B (36.6 mg), fraction C (7.8 mg yield, monomeric procyanidin), fraction D (26.6 mg yield, rich in monomeric and oligomeric procyanidin), and fraction E (18.1 mg yield, rich in polymeric procyanidin). The original MeOH extract administered (100 mg/kg po) produced about 47% inhibition of carrageenin-induced paw oedema 1 h after administration. Fraction D, obtained from the ethylacetate extract and rich in procyanidins produced over 33% inhibition of carrageenan-induced paw oedema while a dose of 19.2 microg/ml produced 100% inhibitory effect on 5-lipoxygenase. A dose of 100 mg/kg of the MeOH extract also produced over 30% reduction of the sensitivity to pain while 50 mg/kg of fraction D rich in procyanidins produced over 45% analgesic effects. These results were judged significant compared to those obtained with indomethacin and acetylsalicylic acid. These findings suggest that extracts of the bark of Erythrophleum suaveolens possess potent anti-inflammatory and analgesic property and that the procyanidins lead to the observable pharmacological effects.     

Immune reconstitution inflammatory syndrome associated with progressive multifocal leukoencephalopathy in a perinatally acquired human immunodeficiency virus-infected young adult

Perinatally infected children represent a large proportion of the youth living with human immunodeficiency virusinfection/acquired immunodeficiency syndrome (HIV/AIDS). Because of nonadherence to treatment, an increasing number of perinatally acquired HIV-infected adolescents and young adults are showing virologic failure and immune suppression. We report a case of progressive multifocal leukoencephalopathy secondary to immune reconstitution inflammatory syndrome in a perinatally HIV-infected young adult, occurred shortly after the revision of an antiretroviral regimen. The patient showed marked improvement with the combination of corticosteroid and antiretroviral treatment.     

Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells

Numerous epidemiological studies have documented that obesity is a risk factor for breast cancer especially in post-menopausal women. However, the molecular basis of this association is not well known. In contrast to leptin, plasma levels of adiponectin, another major adipokine, are decreased in obese subjects. Therefore, we and others hypothesized that adiponectin may be a paracrine factor negatively controlling mammary tumor development. We recently demonstrated growth inhibition of the estrogen-sensitive breast cancer MCF-7 cell line by adiponectin. The purpose of the present study was to determine whether this anti-proliferative effect of adiponectin also applies to the MDA-MB 231 estrogen-insensitive breast epithelial cancer cell line. Our results demonstrate that i) the adiponectin-specific receptors AdipoR1 and R2 are expressed in these cells, and ii) the subphysiological concentrations of recombinant adiponectin inhibit MDA-MB 231 cell growth and concomitantly enhance the expression of Bax and p53, two pro-apoptotic genes. Moreover, the invalidation of AdipoR1 and R2 mRNA experiments demonstrated that the anti-proliferative and pro-apoptotic effects of adiponectin were partially mediated via AdipoR1 and R2. We describe, for the first time, that AdipoR mRNA expression was down-regulated by adiponectin and leptin in MDA-MB 231 cells. Taken altogether, these results strongly suggest that the two adipokines should be considered as i) additional factors of breast cancer risk, and ii) may therefore be potential targets in breast cancer therapy.     

Pseudoxanthoma elasticum: clinical, histologic, and genetic studies--a report of two sisters

CASE 1: A 24-year-old black woman was referred to our clinic in September 1999 by the department of dermatology. She was referred to confirm the diagnosis of pseudoxanthoma elasticum (PXE). Her medical history was normal. Dermatologic examination revealed confluent papules that gave the skin a "plucked chicken" appearance on the flexural surfaces in the neck, axillae, clavicle, thigh, and periumbilical area (Figure 1). The patient stated that the changes in her skin had begun in the periumbilical region at about 5 years of age and had since been slowly progressive. Physical examination showed brownish black pigmentation on the left side of the face, left eyelid, and left sclera, which was diagnosed as Nevus of Ota (Figure 2). Her visual acuity was 20/10 in both eyes, with no afferent pupillary defect. Intraocular pressure in both eyes was normal. Slit lamp examination showed no abnormalities. Findings from fundus examination revealed angioid streaks that formed an incomplete ring around the optic disc and anteriorly radiated toward the equator of the globe, multiple calcified drusen-like structures, and "peau d'orange" changes. Skin biopsy (skin tissue from the neck) was taken and the diagnosis of PXE was confirmed. Histopathologic findings revealed calcification of the elastic fibers and abnormalities of the collagen (Figure 3). The patient was not known to have sickle cell anemia or sickle cell trait, and her blood pressure levels had never elevated. Other systemic causes of angioid streaks were excluded by findings from extensive laboratory examination. Her relatives were asked to come in for examination but lived far away. One of the patient's sisters lived in Kinshasa, Africa, however, and is presented in case 2. CASE 2: The 27-year-old sister of the previous patient was examined on April 19, 2000. At examination, she was found to have PXE. Her medical history was significant for systemic hypertension since 1998 and genital hemorrhage. She underwent an ablation of a cyst of her left ovary in 1988. Her ocular history was unremarkable. On physical examination, raised (yellow) papillary lesions, typical of pseudoxanthoma, were found on the neck, axillae, clavicle, thigh, and periumbilical regions. External and anterior segment examinations (of her eyes) were unremarkable. She was found to have a best-corrected visual acuity of 20/10 in both eyes. Intraocular pressure was normal. Funduscopy revealed bilateral angioid streaks, crystalline bodies, and "peau d'orange," but to a lesser extent than in her sister. In both cases, after informed consent, peripheral blood cells were taken and sent for extraction of DNA. Analysis was performed but could not demonstrate the known gene defects of PXE.     

The child with an acute limp

The limping child is a common presentation to the emergency department. When confronted with a crying child who cannot walk or explain why, a structured approach based on an appreciation of the underlying physiology can help identify those children with (sometimes subtle) red flags, avoid unnecessary interventions and hospital stays. Here we discuss the differential diagnosis of an acute atraumatic limp, and suggest an approach to examination and investigation, including some key pitfalls and signs to look out for.     

Evaluation of Cobas Integra 800 under simulated routine conditions in six laboratories.

The new selective access analyser Cobas Integra 800 from Roche Diagnostics was evaluated in an international multicentre study at six sites. Routine simulation experiments showed good performance and full functionality of the instrument and provocation of anomalous situations generated no problems. The new features on Cobas Integra 800, namely clot detection and dispensing control, worked according to specifications. The imprecision of Cobas Integra 800 fulfilled the proposed quality specifications regarding imprecision of analytical systems for clinical chemistry with few exceptions. Claims for linearity, drift, and carry-over were all within the defined specifications, except urea linearity. Interference exists in some cases, as could be expected due to the chemistries applied. Accuracy met the proposed quality specifications, except in some special cases. Method comparisons with Cobas Integra 700 showed good agreement; comparisons with other analysis systems yielded in several cases explicable deviations. Practicability of Cobas Integra 800 met or exceeded the requirements for more than 95% of all attributes rated. The strong points of the new analysis system were reagent handling, long stability of calibration curves, high number of tests on board, compatibility of the sample carrier to other Roche systems, and the sample integrity check for more reliable analytical results. The improvement of the workflow offered by the 5-position rack and STAT handling like on Cobas Integra 800 makes the instrument attractive for further consolidation in the medium-sized laboratory, for dedicated use of special analytes, and/or as back-up in the large routine laboratory.     

Sexual behaviors and procreational intentions of adolescents and young adults with perinatally acquired human immunodeficiency virus infection: Experience of an urban tertiary center

PurposeTo assess sexual knowledge, behaviors, and procreational intentions of adolescents and young adults with perinatally acquired human immunodeficiency virus (PNA HIV) infection. Increasingly, children with PNA HIV infection survive to adolescence and become sexually active. Understanding their procreational intentions could aid in designing reproductive health and secondary prevention programs.MethodsA cross-sectional survey of adolescents and young adults with PNA HIV infection at an urban tertiary center was conducted. From June 2003 through September 2004, participants completed a questionnaire that inquired about their sexual knowledge and behaviors. Participants aware of their diagnoses also completed items regarding procreational intentions.ResultsSeventy-four percent (57/77) of eligible participants completed the survey. Thirty-three percent (19/57) of participants reported having had penile–vaginal intercourse, 89.4% of them after learning of their HIV status. Fifty percent (5/10) of sexually active female participants had been pregnant. Among the 50 participants who were aware of their diagnosis, 70% (n = 35) expressed intent to have children. A majority of those aware of the risk of maternal-to-child transmission (MTCT) (71.1%) expressed intent to procreate. Participants who perceived MTCT as low were more likely to express intent to procreate than those who perceived the risk of MTCT as high.ConclusionsAdolescents with PNA HIV infection are becoming sexually active and express intent to have children. This has important implications for secondary prevention of HIV infection. These adolescents need innovative intervention programs offering reproductive health education including procreational choices and considerations.     

Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.     

Kainate receptor-mediated synaptic currents in cerebellar Golgi cells are not shaped by diffusion of glutamate

We report the presence of kainate receptors (KARs) in cerebellar Golgi cells of wild-type but not GluR6-deficient mice. Parallel fiber stimulation activates KAR-mediated synaptic currents [KAR-excitatory postsynaptic currents (EPSCs)] of small amplitude. KAR-EPSCs greatly differ from synaptic currents mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors (AMPAR-EPSCs) at the same synapse. KAR-EPSCs display slow rise and decay time and summate in response to a train of stimulations. By using PDA, a low-affinity competitive antagonist and agents that modify the clearance of glutamate, we show that these properties cannot be explained by diffusion of glutamate outside of the synaptic cleft and activation of extrasynaptic KARs. These data suggest that the slow kinetic of KAR-EPSCs is due to intrinsic properties of KARs being localized at postsynaptic sites. The contrasting properties of KAR- and AMPAR-EPSCs in terms of kinetics and summation offer the possibility for a glutamatergic synapse to integrate excitatory inputs over two different time scales.     

Susceptibility of Grammomys surdaster thicket rats to Trypanosoma brucei gambiense infection

Human African Trypanosomiasis is caused by Trypanosoma brucei gambiense and T. b. rhodesiense. Historically, a treatment relapse rate of about 5% is observed in patients treated with melarsoprol, an arsenical derivative used for treatment of both gambiense and rhodesiense second stage sleeping sickness. More recently, relapse rates up to 30% are noted in gambiense sleeping sickness foci in Angola, Sudan and Uganda. Therefore, WHO established a Network on Treatment Failure and Drug Resistance in Sleeping Sickness. One of its objectives is to improve isolation of T. b. gambiense from relapsing cases for research on drug resistance mechanisms. Trypanosoma b. gambiense isolation techniques suffer from low success rates and long periods needed to adapt the parasite to its new host. Usually, rodents are inoculated with patient's blood or cerebrospinal fluid and sub-passaged until the strain becomes sufficiently adapted to yield high parasitaemia within few days after inoculation. Until now, the best recipient for T. b. gambiense is Mastomys natalensis, with a success rate of about 50%. In this study, Grammomys surdaster (former Thamnomys surdaster) was investigated as a potential recipient for isolation of T. b. gambiense. Comparative experimental infections of Swiss mice, Wistar rats and G. surdaster thicket rats with T. b. gambiense clearly show that this trypanosome grows faster in G. surdaster. Inoculation of the same rodent species with patient's blood and cerebrospinal fluid in Kinshasa (R.D. Congo) confirms the observation that the thicket rats are more susceptible to T. b. gambiense infection than typical laboratory rodents.