Mutagenic and cytotoxic effect of planifolin: a naphthopyranone dimer isolated from Paepalanthus planifolius.

A naphthopyranone dimer, named planifolin, was isolated from a methylene chloride extract of the capitula of Paepalanthus planifolius Koern. The molecule (C(31)H(26)O(10)) appeared to be made up of two monomeric portions, semi-vioxanthin and paepalantine (an isocoumarin), linked by an ether bond, and it may possess several kinds of biological activity that can be related to its polyphenolic structure. Short-term tests that detect genetic damage can afford the information needed to evaluate carcinogenic risks of chemicals to humans. The Ames test, recommended for testing the mutagenicity of chemical compounds with potential pharmacological application, was used in the present study. The mutagenic activity was evaluated in Salmonella typhimurium strains TA100, TA98, TA102 and TA97a and the cytotoxic effect in McCoy cells. The in vitro cytotoxicity of planifolin to McCoy cells, tested in microculture with neutral red, showed a significant cytotoxic index (CI(50)) of 12.83 microg/mL. Planifolin showed mutagenic activity for TA100, TA98 and TA97a. The results indicate that this new naphthopyranone dimer causes mutations by substitution and by addition and deletion of bases in the sequence of DNA. Moreover, its mutagenic potential was increased by metabolic activation.     

抗CD20单抗（Rituximab）作为B细胞淋巴瘤老龄患者初始治疗的新标准

背景侵袭性B细胞淋巴瘤是目前最常见的非霍奇金淋巴瘤类型,主要包括弥漫大B细胞淋巴瘤(DLBCL)和套细胞淋巴瘤(MCL)。超过60%的患者被诊断出B细胞淋巴瘤时年龄都在60岁以上。在过去的30年间,CHOP方案(环磷酰胺、多柔比星、长春新碱、泼尼松)是治疗DLBCL的金标准。年龄较轻的患者     

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Background

Iron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 μg/L).

Methods

Single blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α ₁-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α ⁺-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.

Results

Individually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.

Conclusions

Erythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.

Trial registration

NCT01308112 (2 March 2011).

     

Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions

Purpose

Treatment of large cartilage lesions of the knee in weight-bearing areas is still a controversy and challenging topic. Autologous osteochondral mosaicplasty has proven to be a valid option for treatment but donor site morbidity with most frequently used autografts remains a source of concern. This study aims to assess clinical results and safety profile of autologous osteochondral graft from the upper tibio-fibular joint applied to reconstruct symptomatic osteochondral lesions of the knee.

Methods

Thirty-one patients (22 men and 9 women) with grade 4 cartilage lesions in the knee were operated by mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint, between 1998 and 2006. Clinical assessment included visual analog scale (VAS) for pain and Lysholm score. All patients were evaluated by MRI pre- and post-operatively regarding joint congruency as good, fair (inferior to 1 mm incongruence), and poor (incongruence higher than 1 mm registered in any frame). Donor zone status was evaluated according to specific protocol considering upper tibio-fibular joint instability, pain, neurological complications, lateral collateral ligament insufficiency, or ankle complaints.

Results

Mean age at surgery was 30.1 years (SD 12.2). In respect to lesion sites, 22 were located in weight-bearing area of medial femoral condyle, 7 in lateral femoral condyle, 1 in trochlea, and 1 in patella. Mean follow-up was 110.1 months (SD 23.2). Mean area of lesion was 3.3 cm² (SD 1.7), and a variable number of cylinders were used, mean 2.5 (SD 1.3). Mean VAS score improved from 47.1 (SD 10.1) to 20.0 (SD 11.5); p = 0.00. Similarly, mean Lysholm score increased from 45.7 (SD 4.5) to 85.3 (SD 7.0); p = 0.00. The level of patient satisfaction was evaluated, and 28 patients declared to be satisfied/very satisfied and would do surgery again, while 3 declared as unsatisfied with the procedure and would not submit to surgery again. These three patients had lower clinical scores and kept complaints related to the original problem but unrelated to donor zone. MRI score significantly improved at 18–24 months comparing with pre-operative (p = 0.004). No radiographic or clinical complications related to donor zone with implication in activity were registered.

Conclusions

This work corroborates that mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint is effective to treat osteochondral defects in the knee joint. No relevant complications related to donor zone were registered.

Level of evidence

Case series, Level IV.     

Neurotensin modulates synaptic transmission in the nucleus of the solitary tract of the rat

Whole-cell patch clamp recordings were made from neurons of the rat subpostremal region of the nucleus tractus solitarius (NTS) in transverse brainstem slices. Neurotensin (NT) enhanced the firing rate of action potentials from 0.8 +/- 0.4 Hz in control to 1.9 +/- 1.3 Hz (n = 9) and increased their decay time. The peak amplitude of the after-hyperpolarization was decreased by 34+/-5% (n = 9). These effects were associated with a depolarization of 4 +/- 1 mV (n = 10) in the resting membrane potential and an increase in the input resistance (from 768 +/- 220 MOmega to 986+/-220 MOmega; n = 5) and were compensated by manually hyperpolarizing the cell to control values. In voltage clamp experiments NT decreased an outward current (from 488 +/- 161 to 340 +/- 96 pA at +40 mV; n = 5) which reversed near the potassium equilibrium potential. In addition, NT increased the frequency of both excitatory and inhibitory spontaneous synaptic currents, an effect blocked by tetrodotoxin, and did not change the evoked excitatory or inhibitory postsynaptic currents. The selective NTR1 receptor antagonist SR48692 reversibly blocked the effects of NT on both action potentials and spontaneous synaptic currents. Our results suggest that NTR1 receptors can modulate post-synaptic responses in neurons of the subpostremal NTS by increasing cell excitability as a result of blockade of a potassium conductance.