Mycophenolate mofetil as maintenance therapy for proliferative lupus nephritis: a long-term observational prospective study

Introduction  

While the role of mycophenolate mofetil (MMF) in the management of lupus nephritis has been increasingly recognized, limited information is available regarding its efficacy and safety as a long-term maintenance treatment. The aim of the present study was to evaluate the efficacy and safety profile of MMF as maintenance therapy for proliferative lupus nephritis.     

Dental Eruption Sequences in Fossil Colobines and the Evolution of Primate Life Histories

Unlike other catarrhines, colobines show early molar eruption relative to that of the anterior dentition. The pattern is variable, with Asian genera (Presbytina) showing a greater variability than the African genera (Colobina). The polarity of early relative molar eruption, as well as the degree to which it is related to phylogeny, are unclear. Schultz (1935) suggested that the trend reflects phylogeny and is primitive for catarrhines. More recently, however, researchers have proposed that life history and dietary hypotheses account for early relative molar eruption. If the colobine eruption pattern is primitive for catarrhines, it implies that cercopithecines and hominoids converged on delayed relative molar eruption. Alternatively, if the colobine condition is derived, factors such as diet and mortality patterns probably shaped colobine eruption patterns. Here we update our knowledge on eruption sequences of living colobines, and explore the evolutionary history of the colobine dental eruption pattern by examining fossil colobine taxa from Eurasia (Mesopithecus) and Africa (Kuseracolobus aramisi and Colobus sp.) and the basal cercopithecoid Victoriapithecus macinnesi. We scored specimens per Harvati (2000). The Late Miocene-Early Pliocene Mesopithecus erupts the second molar early relative to the incisors, while the Early Pliocene Kuseracolobus aramisi does not. These results demonstrate that the common colobine tendency for early molar eruption relative to the anterior dentition had appeared by the Late Miocene, and that some of the diversity observed among living colobines was already established in the Late Miocene/Early Pliocene. We discuss the implications of these results for phylogenetic, life history, and dietary hypotheses of dental development.     

p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway

Clearance of fibrin through proteolytic degradation is a critical step of matrix remodeling that contributes to tissue repair in a variety of pathological conditions, such as stroke, atherosclerosis, and pulmonary disease. However, the molecular mechanisms that regulate fibrin deposition are not known. Here, we report that the p75 neurotrophin receptor (p75^NTR), a TNF receptor superfamily member up-regulated after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1). We have discovered a new mechanism in which phosphodiesterase PDE4A4/5 interacts with p75^NTR to enhance cAMP degradation. The p75^NTR-dependent down-regulation of cAMP results in a decrease in extracellular proteolytic activity. This mechanism is supported in vivo in p75^NTR-deficient mice, which show increased proteolysis after sciatic nerve injury and lung fibrosis. Our results reveal a novel pathogenic mechanism by which p75^NTR regulates degradation of cAMP and perpetuates scar formation after injury.     

A comparative volumetric analysis of the amygdaloid complex and basolateral division in the human and ape brain

The amygdaloid complex functions to facilitate effective appraisal of the social environment and is an essential component of the neural systems subserving social behavior. Despite its critical role in mediating social interaction, the amygdaloid complex has not attracted the same attention as the isocortex in most evolutionary analyses. We performed a comparative analysis of the amygdaloid complex in the hominoids to address the lack of comparative information available for this structure in the hominoid brain. We demarcated the amygdaloid complex and the three nuclei constituting its basolateral division, the lateral, basal, and accessory basal nuclei, in 12 histological series representing all six hominoid species. The volumes obtained for these areas were subjected to allometric analyses to determine whether any species deviated from expected values based on the other hominoids. Differences between groups were addressed using nonparametric comparisons of means. The human lateral nucleus was larger than predicted for an ape of human brain size and occupied the majority of the basolateral division, whereas the basal nucleus was the largest of the basolateral nuclei in all ape species. In orangutans the amygdala and basolateral division were smaller than in the African apes. While the gorilla had a smaller than predicted lateral nucleus, its basal and accessory basal nuclei were larger than predicted. These differences may reflect volumetric changes occurring in interconnected cortical areas, specifically the temporal lobe and orbitofrontal cortex, which also subserve social behavior and cognition, suggesting that this system may be acted upon in hominoid and hominid evolution.     

Mechanism of the formation of DNA-protein cross-links by antitumor cisplatin

DNA–protein cross-links are formed by various DNA-damaging agents including antitumor platinum drugs. The natures of these ternary DNA–Pt–protein complexes (DPCLs) can be inferred, yet much remains to be learned about their structures and mechanisms of formation. We investigated the origin of these DPCLs and their cellular processing on molecular level using gel electrophoresis shift assay. We show that in cell-free media cisplatin [cis-diamminedichloridoplatinum(II)] forms DPCLs more effectively than ineffective transplatin [trans-diamminedichloridoplatinum(II)]. Mechanisms of transformation of individual types of plain DNA adducts of the platinum complexes into the DPCLs in the presence of several DNA-binding proteins have been also investigated. The DPCLs are formed by the transformation of DNA monofunctional and intrastrand cross-links of cisplatin. In contrast, interstrand cross-links of cisplatin and monofunctional adducts of transplatin are stable in presence of the proteins. The DPCLs formed by cisplatin inhibit DNA polymerization or removal of these ternary lesions from DNA by nucleotide excision repair system more effectively than plain DNA intrastrand or monofunctional adducts. Thus, the bulky DNA–protein cross-links formed by cisplatin represent a more distinct and persisting structural motif recognized by the components of downstream cellular systems processing DNA damage considerably differently than the plain DNA adducts of this metallodrug.     

<Emphasis Type="Italic">Daphnia galeata</Emphasis> in the deep hypolimnion: spatial differentiation of a “typical epilimnetic” species

One of the most serious threats to tropical mangrove ecosystems caused by shrimp farming activities is the poor management of pond waste materials. We hypothesise that mangroves can tolerate chemical residues discharged from shrimp farms and can be used as biofilters, but the capability of mangroves to cope with solid sediments dredged from shrimp ponds is limited. Our study in Pak Phanang, Thailand, confirmed that the excess sediments discharged from nearby shrimp ponds reduced mangrove growth rates and increased mortality rates. A series of transformed multi-temporal satellite images was used in combination with the field data to support this claim. In addition, a comparison between four dominant mangrove species revealed that Avicennia marina could tolerate sedimentation rates of >6 cm year⁻¹, while Bruguiera cylindrica tolerated sedimentation rates of 5 cm year⁻¹ (total sediment depth = 25 cm) before dying, while Excoecaria agallocha and Lumnitzera racemosa performed intermediate. This outcome implied that in our situation A. marina and to lesser extent E. agallocha and L. racemosa could be more effective as biofilters than B. cylindrica, as they may survive the sedimentation longer in the disposal areas. Further studies on the impact of sedimentation and chemical pollution of shrimp farm wastes on mangrove mortality and growth are required.     

Berry fruits as a source of biologically active compounds: the case of Lonicera caerulea

Background: Lonicera caerulea L. (blueberry honeysuckle, Caprifoliaceae) is a traditional crop in northern Russia, China, and Japan. Its fruits are little known as edible berries in North America and Europe. This review deals with the botany and chemical composition of L. caerulea and the biological activity of its main constituents, focusing on the potential health benefits of the berries. Methods and Results: PubMed, Science Direct and ISI Web of Knowledge(SM) databases were used for this paper. Literature sources include the period 1935-2007. L. caerulea berries a are rich source of phenolic compounds such as phenolic acids as well as anthocyanins, proanthocyanidins and other flavonoids, which display potential health promoting effects. Chemopreventive, antimicrobial, anti-adherence and antioxidant benefits, among others are described for these compounds. Conclusions: The potential of L. caerulea berries to prevent chronic diseases such as diabetes mellitus, cardiovascular diseases and cancer seems to be related above all to their phenolic content.