Effects of bone morphogenetic proteins on primary human renal cells and the generation of bone morphogenetic protein-7-expressing cells for application in bioartificial kidneys

Bioartificial kidneys (BAKs) contain renal cells, and primary human renal proximal tubule cells (HPTCs) have been applied in clinical trials with BAKs. Cell performance within the device is critical. HPTC performance is often compromised under in vitro conditions because of dedifferentiation, transdifferentiation, and tubule formation on substrate surfaces. Herein we tested whether treatments with human recombinant bone morphogenetic protein (BMP)-2 or BMP-7 would improve HPTC performance. We found that both growth factors improved HPTC performance, but more consistent results were obtained with BMP-7. The effects were strongly concentration dependent, and for BMP-7, 25?ng/mL was the optimal concentration, which improved HPTC performance under static and under bioreactor conditions. As an alternative to supplementation with the purified growth factor, we generated HPTCs secreting human recombinant BMP-7. BMP-7 secreted by the cells was bioactive and improved the functional performance of HPTCs, in agreement with our other findings. Together, the results suggested that either supplementation with purified BMP-7 or BMP-7-producing cells could be used to improve cell performance in BAKs. BAKs with BMP-7-producing cells could also be used to deliver the growth factor to kidney patients. Our results suggested that the amount of BMP-7 produced by HPTCs would be sufficient for therapeutic applications.     

Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: role of nitric oxide and α₁-adrenoceptor mRNA expression

Hyporeactivity to vasoconstrictors is one of the clinical manifestations of sepsis in man and experimental animals. The objective of the investigation was to examine whether atorvastatin can prevent hyporeactivity to norepinephrine (NE) in mouse aorta in sepsis, and if so, what are the mechanisms involved. Sepsis in mice was induced by cecal ligation and puncture. The aorta was harvested for tension experiment, nitric oxide (NO) and cyclic guanosine monophosphate measurements, and inducible NO synthase (iNOS) and α(1D)-adrenoceptor mRNA expression studies. In comparison with sham-operated controls, sepsis significantly decreased the contractile response to NE in the mouse aorta. Pretreatment with atorvastatin of septic animals completely restored NE-induced contractions to levels similar to those of sham-operated controls and significantly increased survival time and mean arterial pressure. Atorvastatin also attenuated iNOS-induced overproduction of NO, as well as iNOS mRNA expression. Accordingly, hyporeactivity to NE was not evident in tissues pretreated with selective iNOS inhibitor 1400W in sepsis. Although basal cyclic guanosine monophosphate accumulation in the aorta was reduced in sepsis, pretreatment of the tissues with soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ) partially restored the reactivity to NE. Interestingly, hyporeactivity to NE in sepsis was associated with a decreased α(1D)-adrenoceptor mRNA expression in the mouse aorta. Atorvastatin pretreatment, however, prevented the decrease in α(1D)-adrenoceptor mRNA expression in septic animals. In conclusion, atorvastatin seems to prevent hyporeactivity to vasoconstrictor NE in the aorta from septic mice through attenuation of overproduction of NO as well as improved α(1D)-adrenoceptor mRNA expression. The findings of the present study may explain the beneficial effects of atorvastatin on improved hemodynamic functions in sepsis.     

Edwards syndrome with double trisomy

Double trisomy is rare and the only case reported in the literature died soon after birth. We present another case of double trisomy (48XYY, +18) in a male neonate, who was born to a 28-year-old gravida three parity one mother at 35 weeks of gestation. The baby had features of trisomy 18. Karyotype of the patient showed 48, XYY, +18, Ish (DYZ3*2), (D18Z1*3), nuc ish (DYZ3*2), (D18Z1*3) . The patient had clinical features of trisomy 18. There was no family history of diabetes mellitus and no exposure to chemicals. It has been suggested that the rarity of Y-chromosome involvement in trisomy 18 may be due to discrepancy between the sexes.     

Biologically active Chitosan/ZnO/Acalypha indica leaf extract biocomposite: An investigation of antibacterial,cell proliferation and cell migration aptitude for wound healing application

A biocomposite composed of Chitosan (Cs), Zinc oxide (ZnO), Acalypha indica (AI) was fabricated by simple chemical precipitation method. The achieved biocomposite was characterized by Fourier Transmission Infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), Scanning electron microscope (SEM) with Energy dispersive X-ray analysis spectroscopy (EDAX) and Transmission electron microscope (TEM). The phytochemical constituents in the AI leaf extract were also studied by Gas chromatography mass spectrometer (GC-MS) analysis. The anti-inflammatory and antioxidant studies were studied using Diclofenac sodium and ascorbic acid as standard by Fetal bovine serum denaturation and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) DPPH radical scavenging method. The effective bactericidal action of the composite was evaluated against both gram-negative, gram-positive bacteria such as Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). The hemolysis activity was studied using Triton x 100 as negative and Phosphate buffer solution (PBS) as positive control. The biocompatibility nature was evaluated by the MTT (3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay and Fluorescence staining method using mouse fibroblast cells (L929). Additionally, the in-vitro wound healing potential was also assessed by scratch wound assay with L929 mouse fibroblast cells. Hence, these obtained results suggest that the Cs/ZnO/AI biocomposite can act as a suitable candidate in wound care applications.