Interactions between human immunodeficiency virus and herpes viruses within the oral mucosa

ABSTRACTThere is evidence from clinical case reports and epidemiological studies that human immunodeficiency virus (HIV) can be transmitted through oral sex. Herpes viruses that appear in the oral mucosa might influence the oral replication of HIV. A review of data suggesting that interactions occur between HIV and herpes viruses indicates that such interactions might operate in the oral mucosa. Defining the mechanisms by which herpes viruses interact with HIV in the oral mucosa should permit intervention measures to be targeted more precisely

Investigating short-time-scale variations in cometary ions around comet 67P

The highly varying plasma environment around comet 67P/Churyumov–Gerasimenko inspired an upgrade of the ion mass spectrometer (Rosetta Plasma Consortium Ion Composition Analyzer) with new operation modes, to enable high time resolution measurements of cometary ions. Two modes were implemented, one having a 4 s time resolution in the energy range 0.3–82 eV/q and the other featuring a 1 s time resolution in the energy range 13–50 eV/q. Comparing measurements made with the two modes, it was concluded that 4 s time resolution is enough to capture most of the fast changes of the cometary ion environment. The 1462 h of observations done with the 4 s mode were divided into hour-long sequences. It is possible to sort 84 per cent of these sequences into one of five categories, depending on their appearance in an energy–time spectrogram. The ion environment is generally highly dynamic, and variations in ion fluxes and energies are seen on time-scales of 10 s to several minutes

Developmental programming: Sex-specific programming of growth upon prenatal bisphenol A exposure

In both human and animals, in utero exposure to bisphenol A (BPA), an endocrine-disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth trajectory were measured in both sexes. Gestational BPA administration resulted in higher accumulation in male than female fetuses only at fetal day 65, with minimal impact on fetal/maternal steroid milieu in both sexes at both time points. BPA-treated male fetuses were heavier than BPA-treated female fetuses at fetal day 90 whereas this sex difference was not evident in the control group. At the organ level, liver weight was reduced in prenatal BPA-treated female fetuses, while heart and thyroid gland weights were increased in BPA-treated male fetuses relative to their sex-matched control groups. Prenatal BPA treatment also altered the postnatal growth trajectory in a sex-specific manner. Males grew slower during the early postnatal period and caught up later. Females, in contrast, demonstrated the opposite growth trend. Prenatal BPA-induced changes in fetal organ differentiation and early life growth strongly implicate translational relevance of in utero contributions to reproductive and metabolic defects previously reported in adult female offspring.Prenatal exposure to bisphenol A from early to mid-gestation leads to sex-specific changes in fetal organ weight and postnatal growth.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151993/1/jat3836.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151993/2/jat3836_am.pd

Progress in the discovery of selective, high affinity A2B adenosine receptor antagonists as clinical candidates

The selective, high affinity A2B adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A2B AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A2B AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, Ki(hA2B) = 22 nM; Ki(hA1) = 1,940 nM; Ki(hA2A) = 3,280; and Ki(hA3) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t1/2 = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A2B AdoR (KB = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi’s group in conjunction with King Pharmaceuticals that has favorable A2B AdoR affinity and selectivity [Ki(hA2B) = 5.5 nM; Ki(hA1) > 1,000 nM; Ki(hA2A) > 1,000; and Ki(hA3) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A2B AdoR affinity and selectivity [Ki(hA2B) = 17 nM; Ki(hA1) > 1,000 nM; Ki(hA2A) > 2,500; and Ki(hA3) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A2B AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A2B AdoR in various disease states will soon be established

Evaluation of the single platform Muse® Auto CD4/CD4 % system in Cameroon

Background: according to who revised guidelines for scaling up antiretroviral therapy (ART) in adults and children living in resource-limited settings, there is an urgent need for laboratory monitoring, including the numeration of CD4 T cells.Objective: the study compared the muse® auto CD4/CD4% System for CD4 t cell enumeration in absolute counts and in percentages, to the Guava® AutoD4/CD4% System.Design: This was a prospective study using adults, adolescents, children and infant’s samples.Setting: The Centre International de Diagnostic Medical (CIDM), Yaounde, a research laboratory devoted to HIV screening and monitoring affiliated to the University of Yaounde I.Subjects: K3-EDTA-blood samples from 111 patients (77 adults, 12 adolescents, 18 children and 4 infants) were collected and tested. All participants signed an informed consent form whereas the guardian and parent of children signed the assent form.Results: the absolute CD4 t lymphocyte counts as well as the percentage CD4 lymphocyte of the Muse® AutoCD4/CD4% and GuavaAutoCD4/CD4% Systems, were highly correlated with an interclass correlation coefficient of 0.997 (95%CI: 0.996-0.998) and 0.991 (95% CI: 0.987-0.994) respectively. The Bland-Altman analysis limits of agreement were -5.79 cells/μl (95%CI: [-97.77; 86.19]) for the absolute CD4 T lymphocyte counts and -1.93 (95%CI: [-7.29; – 3.43]) for CD4 T lymphocyte percentage. The numbers of outliers were similar (6/111=5.41%) both for CD4 T lymphocyte counts and percentage. In addition, Cohen’s Kappa ranged from 0.95 to 1 according to CD4 T lymphocyte counts thresholds (p<0.001), showing agreement between both methods. Conclusion: this study demonstrates that the muse™ auto CD4/CD4% system constitutes a promising system for CD4 t cell counting comparable to existing reference methods, and should facilitate wider access to CD4 T cell enumeration for adults and children with HIV infection living in resource-limited countries

Electrical storm reversible by isoproterenol infusion in a striking case of early repolarization

A 40-year-old woman was referred to intensive care unit after recurrent ventricular fibrillation. She was free of cardiac medical history or medications. The resting ECG displayed an extended early repolarization in the inferior leads and all the precordial leads. Incessant ventricular fibrillations justified a treatment by intravenous amiodarone associated with general anaesthesia and mechanical ventilation without success on ventricular fibrillation. Because of a low heart rate intravenous isoproterenol infusion was initiated. Isoproterenol infusion was associated with heart rate acceleration and a decrease in J point elevation and the disappearance of ventricular fibrillation episodes. No cardiac disease was documented and the patient was implanted of a single chamber ICD. Six months later the patient was free of syncope and ventricular fibrillation on ICD memory. This case report demonstrates the usefulness and efficiency of the isoproterenol infusion to eliminate recurrent ventricular fibrillation in patients with early repolarization

Polyarteritis nodosa presenting as a bladder outlet obstruction

Polyarteritis nodosa (PAN) of the urinary tract is rare. An unusual case of systemic PAN involving the bladder neck is described. A 27-year-old man, with known diastolic hypertension diagnosed 2 years earlier, was admitted with chronic urinary obstruction complicated by hydronephrosis. He had symptoms of myalgia and weight loss, was afebrile but had an elevated erythrocyte sedimentation rate and acute-on-chronic renal impairment. All virological and serological tests including hepatitis B and anti-neutrophil cytoplasmic antibody were negative. A computed tomography scan of the brain revealed small-vessel disease. A bladder neck mass was visualised on cystoscopy. Histological examination of this demonstrated a medium-sized necrotising vasculitis with small-vessel fibrinoid necrosis suggestive of PAN. At least six of the American College of Rheumatology criteria for PAN were met. The patient was treated with pulses of intravenous cyclophosphamide and oral corticosteroids with a good clinical response

<i>Ginkgo biloba</i> extract EGb 761^® alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials.

Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, &lt;i&gt;Ginkgo biloba&lt;/i&gt; extract EGb 761 &lt;sup&gt;®&lt;/sup&gt; was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761 &lt;sup&gt;®&lt;/sup&gt; at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. Randomized, placebo-controlled clinical trials of &lt;i&gt;G. biloba&lt;/i&gt; extract EGb 761 &lt;sup&gt;®&lt;/sup&gt; identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761 &lt;sup&gt;®&lt;/sup&gt; was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for tinnitus ( &lt;i&gt;p&lt;/i&gt; = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness ( &lt;i&gt;p&lt;/i&gt; = 0.03). Our findings support the notion that EGb 761 &lt;sup&gt;®&lt;/sup&gt; is also effective in alleviating concomitant neurosensory symptoms in patients with dementia