Stenocereus huastecorum-fruit juice concentrate protects against cisplatin-induced nephrotoxicity by nitric oxide pathway activity and antioxidant and antiapoptotic effects.

Cisplatin (CP) is an antineoplastic agent used to treat solid tumors, that has high nephrotoxicity caused by physiologic, hemodynamic, and biochemical alterations. Some studies have shown that naturally derived bioactive compounds in CP-induced nephrotoxicity reduce the side effects of this antineoplastic drug. Pitaya is an endemic fruit from Mexico with a high bioactive compound content, including betalains and phenolic compounds, with reports of antioxidant and anti-inflammatory properties. In this study, the aim was to establish the effect of a pitaya juice concentrate (PJC) on CP-induced nephrotoxicity in Wistar male rats through the identification of metabolites, determination of its chemical composition and antioxidant activity, and evaluation of the protective effect of a PJC on CP-induced nephrotoxicity in rats. The PJC showed a high content of betanins with antioxidant activity by an oxygen radical absorbance capacity assay (1299.6 ± 2.80 Trolox equivalents/g). PJC was administered daily (400 mg day-1, p. o.) for 3 days before CP administration until the end of the experiment. On day four, rats were administered a single injection of CP (6 mg kg, i.p.-1) and sacrificed 72 h later. We observed that CP provoked renal dysfunction (1.0 ± 0.1 vs. 0.4 ± 0.07 serum creatinine levels), oxidative stress, a decrease in nitrate and nitrite (NO2¯/NO3¯) levels (0.1 ± 0.08 vs. 0.4 ± 0.3) and activation of apoptosis and immune responses in kidney tissue. In addition, CP treatment induced tubular damage threefold. PJC administration prevented renal dysfunction (0.5 ± 0.06 vs. 1.0 ± 0.1), normalized degenerative structural damage prevented the increase in lipoperoxidation levels (0.04 ± 0.01 vs. 0.2 ± 0.1) and reduced the apoptosis index by 2.5 in kidney tissue. However, it did not modify the immune response caused by CP. Furthermore, PJC treatment increased nuclear factor erythroid two related factors two protein levels two times and NO2¯/NO3¯ levels 22 times in kidney tissue, which may play a role in the renoprotective effect. In conclusion, the renoprotective effect of PJC on CP-induced nephrotoxicity was associated with the attenuation of dysfunction, structural damage, apoptosis activation, and oxidative stress and was related to changes in the tumor necrosis factor-alpha and renal nitric oxide (NO) pathways. The changes in the NO pathway may be involved in renal hemodynamics. Pitaya could be used as a functional food and therapeutic coadjuvant during CP treatments due to its high bioactive levels and renoprotective compounds.

Influence of C=O groups on the optical extinction coefficient of graphene exfoliated in liquid phase.

Liquid phase exfoliation of graphite is currently one of the most promising graphene production methods at large scale. For this reason, an accurate calculation of the concentration in graphene dispersions is important for standardization and commercialization. Here, graphene dispersions, at high concentrations, were produced by electrochemical exfoliation. Furthermore, a cleaner methodology to obtain graphene oxide by electrochemical exfoliation at high acid concentrations was implemented. The absorption coefficient for graphene and graphene oxide was determined in the optical range (α660 nm= 1414 (±3%) ml mg-1 m-1andα660 nm= 648 (±7%) ml mg-1 m-1, respectively) with an exponential dependence with the wavelength. The difference inαfor both materials is attributed to an increased presence of C=O groups as evidenced by Fourier transform infrared spectroscopy (FTIR), UV-vis and Raman spectroscopy, as well as, in the calculation of the optical extinction coefficient and optical band-gap via Tauc-plots.

[Intrarenal smooth muscle: histology of a complex urodymamic machine]. / Músculo liso intrarrenal: histología de una compleja máquina urodinámica.

OBJECTIVE: To know better the microscopic arrangement of the bundles of smooth muscle in the human renal parenchyma, their distribution and anatomical relationships, trying to make a reconstruction of this muscular system. METHODS: Five adult human kidneys and one fetal kidney were processed "in toto" with cross sections every 300µm. In the histological sections we identify the smooth muscle fibers trying to determine its insertion, course and anatomical relationship with other structures of the kidney tissue. RESULTS: There are bundles of smooth muscle fibers of variable thickness parallel to the edges of the medullary pyramids, bundles that surrounding the medulla in a spiral course, and bundles that accompany arcuate vessels, the latter being the most abundant and easy to identify. These groups of muscle fibers do not have a precise or constant insertion site, their periodicity is not homogeneous and they are not a direct extension of the muscle of the renal pelvis, although some bundles are in contact with it. There are also unusual and inconstant small muscle fibers no associated to vessels in the interstitium of the cortex and, exceptionally, in the medulla. CONCLUSION: There is a complex microscopic system of smooth muscle fibers that partially surround the renal medulla and are related to renal pelvic muscles without a direct continuity with them. Although this small muscular system is under-recognized, could be very important in urodynamics.

Targeted disruption of the transition protein 2 gene affects sperm chromatin structure and reduces fertility in mice.

During mammalian spermiogenesis, major restructuring of chromatin takes place. In the mouse, the histones are replaced by the transition proteins, TP1 and TP2, which are in turn replaced by the protamines, P1 and P2. To investigate the role of TP2, we generated mice with a targeted deletion of its gene, Tnp2. Spermatogenesis in Tnp2 null mice was almost normal, with testis weights and epididymal sperm counts being unaffected. The only abnormality in testicular histology was a slight increase of sperm retention in stage IX to XI tubules. Epididymal sperm from Tnp2-null mice showed an increase in abnormal tail, but not head, morphology. The mice were fertile but produced small litters. In step 12 to 16 spermatid nuclei from Tnp2-null mice, there was normal displacement of histones, a compensatory translationally regulated increase in TP1 levels, and elevated levels of precursor and partially processed forms of P2. Electron microscopy revealed abnormal focal condensations of chromatin in step 11 to 13 spermatids and progressive chromatin condensation in later spermatids, but condensation was still incomplete in epididymal sperm. Compared to that of the wild type, the sperm chromatin of these mutants was more accessible to intercalating dyes and more susceptible to acid denaturation, which is believed to indicate DNA strand breaks. We conclude that TP2 is not a critical factor for shaping of the sperm nucleus, histone displacement, initiation of chromatin condensation, binding of protamines to DNA, or fertility but that it is necessary for maintaining the normal processing of P2 and, consequently, the completion of chromatin condensation.

Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development.

Mutations were introduced into conserved steroidogenic factor 1 (SF1)- and SOX9-binding sites within the endogenous mouse Mullerian inhibiting substance (Mis) promoter. Male mice homozygous for the mutant SF1-binding site correctly initiated Mis transcription in fetal testes, although at significantly reduced levels. Surprisingly, sufficient MIS was produced to eliminate the MUllerian ducts. In contrast, males homozygous for the mutant SOX9-binding site did not initiate Mis transcription, resulting in pseudohermaphrodites. These studies suggest an essential role for SOX9 in the initiation of Mis transcription, whereas SF1 appears to act as a quantitative regulator of Mis transcript levels, perhaps for influencing non-Mullerian duct tissues. Comparative studies of Mis expression in vertebrates indicate that the Mis promoter receives transcriptional inputs that vary between species but result in the same functional readout.

Domain structure of an N-ethylmaleimide-sensitive fusion protein involved in vesicular transport.

N-Ethylmaleimide-sensitive fusion protein (NSF) is an essential component for protein transport between Golgi cisternae. Sequence analysis and proteolytic dissection reveal that NSF contains two tandem "ATP domains," each containing the consensus sequence for the binding of nucleotide. When Escherichia coli-produced Chinese hamster ovary NSF is purified, it exhibits a low, but significant, ATPase activity. The ATPase activity of NSF is sensitive to N-ethylmaleimide and influenced by monoclonal antibodies against recombinant NSF.

IL-1, IL-6, and PDGF mRNA expression in alveolar cells following stimulation with a tobacco-derived antigen.

To test the hypothesis that inflammatory cytokine production might be an early event in the development of the disease associated with smoking, we used alveolar cells from healthy nonsmokers stimulated with TGP as a model system. TGP, a phenol-rich glycoprotein which is present in tobacco leaves and cigarette smoke condensate, activates the immune system. It stimulates polyclonal B cell differentiation, induces primarily an IgE response, and activates human leukocytes to produce IL-1. Using in situ nucleic acid hybridization we show that the steady-state levels of IL-1 alpha, IL-1 beta, IL-6, platelet-derived growth factor (PDGF)-A, and PDGF-B mRNAs are consistently elevated in the alveolar cells of all donors following TGP stimulation. The kinetics of mRNA expression suggest that IL-1 alpha and IL-1 beta mRNAs are independently regulated in alveolar cells, while the regulation of PDGF-A and PDGF-B mRNA seems to be similar. The activated cells also synthesize elevated levels of IL-1 and IL-6. These findings lend support to the suggestion that some clinical consequences of smoking might be initiated and enhanced by the production of inflammatory cytokines. Moreover, IL-6 could also activate a polyclonal B cell response, which could lead to the synthesis of autoantibodies and thus cause immune-mediated tissue injury.