Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor of the transforming growth factor-β superfamily. Members of this protein family are involved in the development of various ...mammalian tissues, including the inner ear. As their notations indicate, they also have well-known effects on bone formation and regeneration. In this study, we examined the influence of rhBMP-2 on spiral ganglion (SG) neurite growth in vitro and showed the presence of its most preferred receptor BMPR-IB in spiral ganglion cells both in vitro and in vivo. SG explants of postnatal day 4 rats were analysed for neurite length and number after organotypical cell culture for 72 h, fixation and immunolabeling. Different concentrations of rhBMP-2 were used in a serum-free culture media. Neurite growth was compared with control groups that lacked stimulative effects; with neutrophin-3 (NT-3), which is a well-established positive stimulus on neurite length and number; and with combinations of these parameters. The results display that neurite number and total neurite length per explant in particular concentrations of rhBMP-2 increased by a maximum factor of two, while the mean neurite length was not affected. NT-3 demonstrated a much more potent effect, delivering a maximum increase of a factor of five. Furthermore, a combination of both growth factors shows a predominant effect on NT-3. Immunohistological detection of BMPR-IB was successful both in cell culture explants and in paraffin-embedded sections of animals of different ages. The results show that rhBMP-2 is, among other growth factors, a positive stimulus for SG neurite growth in vitro. Most growth factors are unstable and cannot be attached to surfaces without loss of their biological function. In contrast, rhBMP-2 can be attached to metal surfaces without loss of activity. Our findings suggest in vivo studies and a future clinical application of rhBMP-2 in cochlear implant technology to improve the tissue/electrode interface.
OBJECTIVESWe tested the effect of kidney-specific multidrug resistance-related protein (MRP2, ABCC2) deficiency on renal organic solute disposition as well as on renal protein and gene expression. ...Furthermore, we investigated whether a particular kidney donor ABCC2 genotype is associated with delayed graft function in patients.
METHODSA new MRP2-deficient rat strain was established. Renal cross-transplantations were performed between congenic MRP2-deficient and wild-type rats. Renal disposition of MRP2 substrates was investigated in native and transplanted rats. Proteomic analyses and transcriptional profiling were performed in rat kidney graft cortices. Ninety-eight human kidney donor–recipient pairs were genotyped for five ABCC2 polymorphisms. The relationship between delayed graft function and ABCC2 genetic variants in donors and recipients was analyzed by backward stepwise logistic regression.
RESULTSIn rats, the absence of renal MRP2 reduced renal bilirubin glucuronide excretion at pathologic plasma concentrations, modified renal p-aminohippurate excretion and did not affect renal morphine-6-glucuronide excretion. Renal MRP2 deficiency led to renal cortical protein or mRNA upregulation of glutathione transferase isoenzymes, glutaredoxin 2, and heme oxygenase-1. In patients, a particular donor ABCC2 genotype was associated with an increased incidence of delayed graft function.
CONCLUSIONKidney graft-specific MRP2 deficiency has mild effects on the renal excretion of some organic solutes under experimental conditions and induces a protein and gene expression pattern indicative of activated antioxidant defense mechanisms. This suggests that MRP2 is a determinant of the redox status in tubular epithelial cells and thus of the susceptibility to renal damage under conditions of treatment with multiple drugs and increased oxygen radical formation.
Tonsils are believed to play an important role during the development of the immune system. Although diseases of the tonsils like hypertrophy of the tonsil, acute tonsillitis, chronic tonsillitis or ...peritonsillar abscess are common, little is known about the underlying pathophysiology. Little is known about antimicrobial peptides produced by the tonsils. The human Delta *b-Defensins 1-3 (hBD1-3) are naturally produced 'antibiotics' with antimicrobial activity against different bacteria, fungi, and viruses. The objective of the study was to determine the concentrations for hBD1-3 in different states of diseases of the tonsilla palatina. After tonsillectomy and tissue fixation in formalin, total proteins were isolated from 38 samples (11 hypertrophy of the tonsil, 8 acute tonsillitis, 11 chronic tonsillitis, 8 peritonsillar abscesses). The protein concentration was determined and ELISA for hBD1-3 were performed. We also conducted immunofluorescence double stainings for the co-expression of streptococcus group A and hBD1-3. We could verify a significant difference for the mean hBD1 score of the acute tonsillitis in comparison to the hyperplastic tonsil, the chronic tonsillitis, and the peritonsillar abscess. There was no statistically significant difference in the hBD2 and hBD3 concentrations between the four groups. The immunofluorescence stainings showed that hBD1-3 and the streptococcus group A in the same place. We conclude that in the hyperplastic tonsilla palatina hBD1-3 play an important role. The mouth is constantly faced with a high bacterial load. During a tonsillitis, the hBD1 concentration is lower than in the non-acute infected tonsil because hBD1 is being consumed for fighting the bacterial infection. But, the existence of hBD1-3 in the tonsil cannot prevent the tonsillitis to become chronic.
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