The structure of 180° supernumerary limbs and a hypothesis of their formation

The results of a detailed analysis of 100 supernumerary limbs generated by 180° ipsilateral rotation (on the same limb stump) of regeneration blastemas is presented. The limbs were analyzed in terms of their position of origin, frequency, cartilage structure by Victoria blue staining, and muscle structure by serial sections. Single, double, or triple supernumeraries can be produced at no unique position of origin, although the posterodorsal quadrant was preferred. Four classes of supernumerary limbs were generated by such operations—normal; double dorsal or double ventral; part normal/part mirror imaged; part normal/part inverted in approximately equal frequencies. After amputation of these supernumeraries the same muscle patterns are faithfully regenerated. A hypothesis to explain the production of these abnormal limbs is proposed based on the observed phenomenon of fusion of supernumerary blastemata, but their regenerative behaviour presents problems for current models of pattern formation. Similar results have been obtained with developing limb buds and the relation between development and regeneration is discussed.     

Effect of perfusate pH on coronary flow and adenosine release in isolated rabbit heart

This study was undertaken in an attempt to further understand the relationship between adenosine and H+ ion. Using Langendorff hearts from male rabbits, the perfusion fluid pH was lowered from 7.4 to 7.1 and 6.8 with CO2. A 31 and 86% increase in coronary flow with a simultaneous increase in the release of adenosine by 61 and 128% was observed at pH 7.1 and 6.8, respectively. A direct relationship between adenosine release and coronary flow with a correlation coefficient of 0.99 was found at pH values of 7.4, 7.1, and 6.8. The degradation products of adenosine namely inosine and hypoxanthine were unchanged at 7.1 and 6.8 from 7.4. These data support a role for adenosine in the regulation of coronary flow and suggest a relationship between adenosine and H+ ion.     

Cellular Changes during Renal Failure-Induced Inflammatory Aortic Valve Disease

Background

Aortic valve calcification (AVC) secondary to renal failure (RF) is an inflammation-regulated process, but its pathogenesis remains unknown. We sought to assess the cellular processes that are involved in the early phases of aortic valve disease using a unique animal model of RF-associated AVC.

Methods

Aortic valves were obtained from rats that were fed a uremia-inducing diet exclusively for 2, 3, 4, 5, and 6 weeks as well as from controls. Pathological examination of the valves included histological characterization, von Kossa staining, and antigen expression analyses.

Results

After 2 weeks, we noted a significant increase in urea and creatinine levels, reflecting RF. RF parameters exacerbated until the Week 5 and plateaued. Whereas no histological changes or calcification was observed in the valves of any study group, macrophage accumulation became apparent as early as 2 weeks after the diet was started and rose after 3 weeks. By western blot, osteoblast markers were expressed after 2 weeks on the diet and decreased after 6 weeks. Collagen 3 was up-regulated after 3 weeks, plateauing at 4 weeks, whereas collagen 1 levels peaked at 2 and 4 weeks. Fibronectin levels increased gradually until Week 5 and decreased at 6 weeks. We observed early activation of the ERK pathway, whereas other pathways remained unchanged.

Conclusions

We concluded that RF induces dramatic changes at the cellular level, including macrophage accumulation, activation of cell signaling pathway and extracellular matrix modification. These changes precede valve calcification and may increase propensity for calcification, and have to be investigated further.     

The Effects of Chromium Picolinate and Chromium Histidinate Administration on NF-κB and Nrf2/HO-1 Pathway in the Brain of Diabetic Rats

The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-??B p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n?=?45) and diabetic (n?=?45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8???g elemental chromium (Cr) per day for 12?weeks. Diabetes was induced by streptozotocin injection (40?mg/kg i.p., for 2?weeks) and maintained by high-fat feeding (40?%). Diabetes was associated with increases in cerebral NF-??B and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (I??B??) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-??B and 4-HNE protein adducts and to increase levels of I??B?? and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-??B p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-??B expression and increasing Nrf2 expression in the brain of diabetic rats.     

Role of an N-Terminal Splice Segment in the Activation of the Cation Channel TRPM2 by ADP-Ribose and Hydrogen Peroxide

In the dysfunctional splice variant TRPM2-ΔN, a stretch of 20 amino acids (aa 537–556) is missing within the N-terminal cytosolic tail of the cation channel TRPM2. The ΔN-stretch overlaps with two IQ-like calmodulin-binding domains. Moreover, it contains two PxxP motifs implicated in protein–protein interactions. Here, we constructed variants to test whether any of these motifs may explain why TRPM2-ΔN does not respond to stimulation with either ADP ribose or hydrogen peroxide. Each of the two IQ-motifs could be removed without loss of channel function. Similarly, deletion of either one or both PxxP motifs had no effect. Moreover, the single point mutation D543E associated with bipolar disorder does not change the activation of TRPM2. We conclude that no functional role can be attributed to any of the structural motifs within the ΔN-stretch that may be a spacer segment for other functional sites in the N terminus.     

Serum free prostate-specific antigen and zinc levels in experimental acute pancreatitis

Serum free prostate-specific antigen (fPSA) is the most useful tumor marker for prostatic cancer screening. However, recently, fPSA has also been detected in sera from patients with pancreatic diseases. In addition, it has been shown that zinc (Zn) concentration might change in both serum and tissues in pancreatic disease. In the present study, we measured serum concentrations of fPSA and Zn as possible markers and prognostic factors in an experimental acute-pancreatitis model. Twenty-five female Wistar albino rats were divided into two groups: the control group (n=10) and the experimental group (n=15). Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. The animals were sacrificed 24 h later to detect the concentrations of serum fPSA and Zn. fPSA values were detected to be significantly higher in the experimental group p<0.001). There was also a significant decrease in the serum Zn level of the acute-pancreatitis group (p<0.001). In conclusion, these findings suggested that a combination of these parameters might represent a significant improvement on the diagnostic value of each of them separately and provide a powerful tool for differential diagnosis and prognosis in pancreatic diseases.