Current topical and systemic approaches to treatment of rosacea

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline. Conventionally, 100–200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

Conflicts of interest

None declared.     

Role of hypoxia during nephrogenesis

Mammals develop in a physiologically hypoxic state, and the oxygen tension of different tissues in the embryo is precisely controlled. Deviation from normal oxygenation, such as what occurs in placental insufficiency, can disrupt fetal development. Several studies demonstrate that intrauterine hypoxia has a negative effect on kidney development. As nascent nephrons are forming from nephron progenitors in the nephrogenic zone, they are exposed to varying oxygen tension by virtue of the development of the renal vasculature. Thus, nephrogenesis may be linked to oxygen tension. However, the mechanism(s) by which this occurs remains unclear. This review focuses on what is known about molecular mechanisms active in physiological and pathological hypoxia and their effects on kidney development.     

包膜活性炭吸附血液灌流清除人血浆中毒鼠强的实验

目的:观察包膜活性炭对血浆中毒鼠强的清除率及吸附规律。方法:实验于2004-05/2006-04在军事医学科学院毒物药物研究所国家重点实验室完成。采用包膜活性炭灌流器对毒鼠强血浆样进行血液灌流吸附,在灌流的1,2,3h分别取样,经乙酸乙酯萃取后,用气相色谱氮磷检测器法(GC/NPD)测定其含量并计算清除率。结果:活性炭对毒鼠强的吸附作用在血液灌流1h最高,灌流2h后毒鼠强质量浓度无明显变化。400,200μg/L毒鼠强血液灌流1h清除率分别为(57.83±1.85)%,(48.18±1.81)%。结论:用包膜活性炭吸附剂进行血浆的灌流吸附,能清除大部分毒物,迅速降低血浆中毒鼠强的质量浓度。     

Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy

Single-dose and multiple-rising dose studies of recombinantfollicle stimulating hormone (rFSH) in hypogonadotrophic maleand female volunteers demonstrated that the rate of FSH absorptionafter i.m. injection is higher in men than in women. In theabsence of endogenous FSH, a correlation between serum FSH andbody weight became apparent. The elimination half-life of rFSHwas not different between the sexes and was comparable withurinary FSH. However, the in-vitro bio:immuno ratio of serumFSH was significantly higher after the administration of rFSHthan after urinary FSH. When rFSH was administered daily witha fixed dose, steady state levels were reached within 3-5 days.Serum FSH concentrations increased in a dose-dependent mannerwhen the daily dose was increased weekly over 3 weeks from 75to 225 IU. In hypogonadotrophic women, rFSH induced normal folliculargrowth whereas oestrogen synthesis was impaired. In women pituitarysuppressed by a high-dose oral contraceptive, the daily administrationof 150 IU rFSH for 1 week induced more and larger antral folliclesthan the same regimen with urinary FSH, whereas the serum immunoactiveFSH concentrations measured 24 h after each dosing were similar.It is concluded that even though equal or lower serum immunoactiveFSH concentrations were obtained following the administrationof rFSH compared with urinary FSH, circulating bioactivity FSHconcentrations were higher. Therefore, the conventional ideathat serum immunoreactive FSH correlates positively with themagnitude of the ovarian response should be reconsidered.     

Neutralizing antibodies to interferon-α and circulating interferon in patients with chronic hepatitis C non-responding to pegylated interferon plus ribavirin re-treated by pegylated interferon-α-2a and ribavirin (ANRS HC16 GAMMATRI substudy)

A lack of antiviral response in patients with chronic hepatitis C treated with pegylated (PEG)‐interferon (IFN)‐α‐2a + ribavirin (RIBA) may be explained by neutralizing antibodies to IFN‐α‐2a. The aim of this study was to assess neutralizing antibodies to IFN‐α‐2a and IFN levels in non‐responder patients who were re‐treated by PEG IFN‐α‐2a and RIBA for 12 weeks. Non‐responders to a first‐line treatment of PEG IFN‐α‐2a + RIBA were included for treatment with PEG IFN‐α‐2a (180 µg/week) + RIBA (1,000 mg/day if <75 kg, 1,200 mg otherwise) for 48 weeks. HCV RNA was measured at week 12. IFN levels and neutralizing antibodies to IFN‐α‐2a were measured retrospectively on stored sera at baseline and weeks 4 and 12, using a quantitative sandwich ELISA for neutralizing antibodies to IFN‐α‐2a. Twenty‐three patients were non‐responders and 19 patients were responders at week 12 of the initial phase of the second‐line treatment. Non‐responders and responders did not differ statistically: baseline age (median age 47 vs. 50 years), HCV RNA (median 6.8 vs. 6.4 log₁₀ copies/ml), gender (70% vs. 73% males), genotype (genotype 1: 91% vs. 80%). The median IFN‐α‐2a levels (pg/ml) at weeks 0, 4, and 12 (interquartile range) did not differ between the 19 responders to initial phase of second‐line treatment and the 23 non‐responders: <3.3 (<3.3–371.4), 1457.3 (106.8–3284.8), and 1,652 (90.8–5,000); 84.5 (3.3–277.4), 1407.4 (120.2–2443.4), and 1620.1 (120.2–2287.1), respectively. Among non‐selected consecutive non‐responder patients, re‐treatment with PEG IFN‐α‐2a + RIBA is associated with virological response regardless of the presence of antibody‐mediated resistance to conventional IFN treatment. J. Med. Virol. 82:2027–2031, 2010. © 2010 Wiley‐Liss, Inc.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

Monitoring platelet dependent thrombin generation in mice

Calibrated automated thrombin generation assay was adapted to measure thrombin generation in platelet rich plasma from mice. Vena cava phlebotomy appeared the best technique for blood sampling. The concentration-effect curves of tissue factor and platelet count have been determined. Corn trypsin inhibitor 2 μM inhibits contact activation effectively. Recombinant human thrombomodulin does not inhibit thrombin generation in mouse plasma but activated protein C (20 nM) does. Thrombin generation was dose dependently diminished by low molecular weight heparin and increased by high concentrations of exogenous factor VIII i.e. the assay can detect both hypo- and hypercoagulability.     

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

Evaluation of the procoagulant activity in the plasma of cancer patients using a thrombin generation assay

Introduction

Circulating microparticles are reported to play a role in cancer hypercoagulability. The procoagulant properties of microparticles derive from the amount of tissue factor and/or phosphatidylserine that they can expose. The aim of our study is to assess the procoagulant activity, including microparticles’ activity, in the plasma of newly diagnosed cancer patients with a simple assay, easy to implement in the laboratory.

Material and methods

Newly diagnosed cancer patients (n = 31) before the start of anticoagulant or chemotherapy were compared to matched controls. We used a thrombin generation assay in four conditions: 1: addition of 1pM tissue factor and 4 μM procoagulant phospholipids, 2: without any trigger, 3 and 4: addition of tissue factor or procoagulant phospholipids alone respectively.

Results

When we added only phospholipids, so that thrombin generation is dependent upon endogenous tissue factor, the lag time was significantly shorter in cancer patients. When we added only tissue factor, i.e. made the results dependent upon phospholipids, the endogenous thrombin potential, the peak, and the velocity index were significantly higher and the time-to-peak was significantly shorter. This suggests that the plasma of cancer patients contained a higher activity of endogenous phospholipids and/or tissue factor which may be borne by microparticles.

Conclusion

This new simple methodology can demonstrate a procoagulant activity in the plasma of newly diagnosed cancer patients which can be explained by higher procoagulant phospholipids and tissue factor activity and thus, brings potentially useful information that current coagulation tests cannot provide.