BIOCHEMICAL ALTERATIONS IN ACUTE HUMAN POLIOMYELITIS: ELECTROLYTE PATTERNS AND TRENDS

Pronounced alterations occur in the biochemical findings in acute poliomyelitis. These are derived from three major mechanisms: (a) inefficient pulmonary gaseous exchange, resulting in respiratory acidosis; (b) profound changes in nitrogen metabolism, resulting in decreased serum albumin, tissue destruction, and increased urinary nitrogen; (c) losses of electrolytes through extrarenal channels such as lung and tracheal secretions, sweating, and gastrointestinal disturbances.The extent of these alterations may be defined by appropriate serum and urinary biochemical determinations. These determinations are valuable both from a therapeutic and a prognostic standpoint. They also contribute to further understanding of physiologic and pathologic conditions in acute poliomyelitis.     

Biochemical alterations in acute human poliomyelitis electrolyte patterns and trends

Pronounced alterations occur in the biochemical findings in acute poliomyelitis. These are derived from three major mechanisms: (a) inefficient pulmonary gaseous exchange, resulting in respiratory acidosis; (b) profound changes in nitrogen metabolism, resulting in decreased serum albumin, tissue destruction, and increased urinary nitrogen; (c) losses of electrolytes through extrarenal channels such as lung and tracheal secretions, sweating, and gastrointestinal disturbances. The extent of these alterations may be defined by appropriate serum and urinary biochemical determinations. These determinations are valuable both from a therapeutic and a prognostic standpoint. They also contribute to further understanding of physiologic and pathologic conditions in acute poliomyelitis.     

Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms

We have generated synthetic peptides corresponding to various portions of human osteopontin (OPN) and have immunized rabbits and mice with these peptides to generate polyclonal and monoclonal antibodies specific to human OPN. We then generated six distinct sandwich enzyme-linked immunoabsorbent assay (ELISA) systems by using different pairs of polyclonal and monoclonal antibodies against human OPN. These systems allowed us to detect not only various isoforms and truncated forms of recombinant OPN, but also the glycosylated form of native urinary OPN. Most importantly, tumor-derived OPN was differentially detected by the six ELISA systems. The ELISA systems that we have developed will be useful for clarifying the functional roles for OPN in vivo in various physiologic and pathologic conditions.     

Drugs and nutrition in old age

Drug effects are influenced by physiologic and pathologic changes that occur as a consequence of aging. The elderly may be more disposed to drug-induced nutrient depletion because of chronic illness, inadequate diet and long-term drug use. Digoxin, isoniazid, corticosteroids, diuretics and psychoactive agents pose special hazards to the nutritional status of elderly patients. On the other hand, dietary factors, such as protein levels or vitamin deficiencies, may be important determinants of age-related changes in drug disposition or toxicity.     

Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms

Thrombospondin 1 (TSP1) plays major roles in both physiologic and pathologic tissue repair. TSP1 through its type 1 repeats is a known regulator of latent TGF-β activation and plays a role in wound healing and fibrosis. Binding of the TSP N-terminal domain to cell surface calreticulin in complex with LDL-receptor related protein 1 stimulates intermediate cell adhesion, cell migration, anoikis resistance, collagen expression and matrix deposition in an in vivo model of the foreign body response. There is also emerging evidence that TSP EGF-like repeats alter endothelial cell-cell interactions and stimulate epithelial migration through transactivation of EGF receptors. The mechanisms underlying these functions of TSP1 and the implications for physiologic and pathologic wound repair and fibrosis will be discussed.     

Effect of myelopeptides on physiological and pathological pain

The action of bone marrow low-molecular peptides (myelopeptides) was studied in the models of physiologic and pathologic pain. Myelopeptides were demonstrated to have a pronounced analgetic effect: they increased the latent period of the rats' response in the hot plate test (physiologic pain) and suppressed severe spinal pain syndrome induced by the generator of pathologically enhanced excitation in the dorsal horn of the spinal cord (pathologic pain). In the experiments with naloxone (an opiate receptor blocker) the data on the opiate properties of myelopeptides were further substantiated. The analgetic effect of myelopeptides can be compared to that of morphine and promedol. Myelopeptides even in considerable doses did not have the side effects characteristic of the majority of opiate analgesics. Therefore, they may be recommended for clinical trials.     

Detection of isoelectric profiles of erythropoietin in urine: differentiation of natural and administered recombinant hormones

Erythropoietin (EPO) is normally present in urine at a low concentration (about 1IU/L, i.e., about 10ng/L) for a total protein concentration of at least 50mg/L. A method to study the isoelectric profile of this hormone from 20-ml urine aliquots without previous purification was developed. This method involves isoelectric focusing of the retentate from ultrafiltered urine. Both the ultrafiltration and the isoelectric focusing required precautionary measures to prevent EPO degradation by the proteases that are present in urine. Because classical immunoblotting gave rise to an unspecific detection of various urinary proteins in the focused retentate, it was essential to use the "double-blotting" process developed to solve this problem. Sufficient sensitivity was achieved using amplified chemiluminiscent detection after the blotting membrane was treated with dithiotreitol. The patterns that were revealed from various urinary samples proved to be highly heterogeneous as they were composed of more than 10 isoforms in a pI range of 3.7-4.7. Clear transformation of the patterns was observed in the case of treatment by the recombinant hormone, suggesting that this method can be regarded an efficient tool for indicating recombinant EPO misuse in sports. It may also open new investigations in the field of physiologic or pathologic exploration.     

Mitochondrial involvement in bladder function and dysfunction

Benign bladder pathology resulting from prostatic hypertrophy or other causes is a significant problem associated with ageing in humans. This condition is characterized by increased bladder mass, decreased urinary flow rate, decreased compliance, and these and other changes in bladder function often subject patients to increased risk of urinary tract infection. While the physiologic attributes of benign bladder pathology have been extensively described in humans and in various animal model systems, the biochemical and molecular genetic bases for that pathology have only recently been investigated in detail. Studies demonstrate that mitochondrial energy production and utilization are severely impaired in bladder smooth muscle during benign bladder disease, and to a large extent this realization has provided a rational basis for understanding the characteristic alterations in urinary flow and compliance in bladder tissue. Recent investigations targeting the detailed molecular basis for impaired mitochondrial function in the disease have shown that performance of the organellar genetic system, and to a large extent that of relevant portions of the nuclear genetic system as well, is severely aberrant in bladder tissue. In this article, we discuss the physiologic aspects of benign bladder disease, summarize biochemical evidence for the altered mitochondrial energy metabolism that appears to underlie bladder pathology, review the structure and function of the mitochondrial genetic system, and discuss molecular genetic studies of that system which have begun to provide a mechanistic explanation for the biochemical and physiological abnormalities that characterize the disease. We also discuss areas for further research which will be critically important in increasing our understanding of the detailed causes of benign bladder pathology.     

Angiopoietin-2 plays an important role in retinal angiogenesis

Angiopoietin 2 (Ang2) expression in the retina is increased during physiologic and pathologic neovascularization suggesting that it may be involved. In this study, we used Ang2-deficient mice to test that hypothesis. Mice deficient in Ang2 showed delayed and incomplete development of the superficial vascular bed of the retina, which develops primarily by vasculogenesis, and complete absence of the intermediate and deep vascular beds which develop by angiogenesis. In addition to incomplete retinal vascular development, Ang2-deficient mice showed lack of regression of the hyaloid vasculature, resulting in a phenotype that mimics infants with persistent fetal vasculature (PFV), a relatively common congenital abnormality. Exposure to high levels of oxygen resulted in partial regression of the retinal vessels, indicating that oxygen-induced regression of retinal vessels does not require Ang2. When these oxygen-exposed mice with few retinal vessels were moved to room air, there was no ischemia-induced retinal neovascularization. These data support the hypothesis that Ang2 plays a critical role in physiologic and pathologic angiogenesis, and physiologic, but not oxygen-induced vascular regression. The data also suggest that infants with PFV should be examined for genetic modifications that would be expected to cause perturbations in Tie2 signaling.     

Spinal anesthesia: practical applications.

The recent widespread popularity of spinal anesthesia can be traced to two events. One is the appreciation that, when used for operations below the level of the umbilicus, anesthetically induced physiologic trespass is less with spinal than with general anesthesia. The other is the recognition that modest hypotension with peripheral vasodilation, that may be seen with spinal anesthesia or intravenous infusion of nitroprusside, is, unlike hypotension associated with hypovolemia, unaccompanied by physiologically significant changes in peripheral distribution of cardiac output or changes in the balance between tissue oxygen supply and demand in the myocardium or elsewhere. Spinal anesthesia also has special advantages specific to urinary tract surgery in the geriatric patient.     

Immunohistochemical localization of physiologic urinary proteins in Wistar rats.

Rat physiologic urinary proteins were immunohistochemically localized. In male Wistar rats, urinary protein antigens were present in both hepatic and epithelial cells of the salivary ducts, the coagulating gland, and the prostate gland. In female rats, urinary protein antigens were present in the same proportion of the salivary glands as in males and in the uterine glands, but to a lesser extent than in salivary glands. The results of this study indicate multiple origins of rat urinary proteins. It remains to be determined if female uterine glands contribute to urinary proteins.     

神经酰胺(ceramide)信使途径

生物体内神经酰胺有多种生成途径。作为重要的第二信使,神经酰胺在多种信号转导过程中发挥广泛作用,从而影响细胞生长、增殖、分化、凋亡及损伤等多种生理、病理过程。此机制的发现被认为是近年来信号转导研究的重要进展之一。     

Apoptosis is involved in the senescence of endothelial cells induced by angiotensin II

Vascular endothelial cells have a finite cell lifespan and eventually enter an irreversible growth arrest, cellular senescence. The functional changes associated with cellular senescence are thought to contribute to human aging and age-related cardiovascular disorders, e.g. atherosclerosis. In this study, induction of Angiotensin II (Ang II) promoted a growth arrest with phenotypic characteristics of cell senescence, such as enlarged cell shapes, increased senescence-associated beta-galactosidase (SA-beta-gal) positive staining cell, and depressed cell proliferation. Apoptotic changes were increased in senescent cells, with a small subset of the senescent cells showing aberrant morphology such as pronounced nuclear fragmentation or multiple micronuclei. The results suggest cell apoptosis is possibly an important factor in the process of pathologic and physiologic senescence of endothelial cells as well as vascular aging.     

神经酰胺信使途径

生物体内神经酰胺有多种生成途径。作为重要的第二信使,神经酰胺在多种信号转导过程中发挥广泛作用,从而影响细胞生长、增殖、分化、凋亡及损伤等多种生理、病理过程。此机制的发现被认为是近年来信号转导研究的重要进展之一。     

Iron particle labeling of haematopoietic progenitor cells: an in vitro study

We present a method for labeling bone marrow haematopoietic progenitor cells with iron particles. Labeling was assessed by magnetic resonance imaging and electron microscopy. Labeling with iron particles could allow the following by imaging techniques of haematopoietic cells in physiologic and pathologic conditions such as the engraftment of haematopoietic progenitor cells or the migration of myelomonocytic cells in inflammatory diseases.     

YTHDF1 promotes NLRP3 translation to induce intestinal epithelial cell inflammatory injury during endotoxic shock

Dear editor, Endotoxic shock usually results from infection-induced physiologic,pathologic,and biologic abnormalities (Singer et al.,2016).Undeniably,it is stil...     

Effects of intraarterial, intravenous, and intraluminal neurotensin on canine ileal sodium and water absorption and blood flow

Neurotensin is a regulatory peptide which is found primarily in the ileum and is secreted into the blood and lumen. The physiologic effects of neurotensin are uncertain but in certain pathologic states neurotensin increases to levels which can have effects on many organs. The effects of intravenous, intraarterial and intraluminal neurotensin (0.075-7.5 micrograms/min) on fed canine ileal sodium and water fluxes, potassium secretion, and blood flows were studied. Intravenous and intraarterial infusion of neurotensin increased net sodium, potassium, and water secretion, due to increased secretory fluxes, and increased hematocrits. Intraarterial neurotensin was not more effective than intravenous neurotensin except for stimulating potassium secretion. Neurotensin increased potassium secretion at 0.075 micrograms/min IA, increased sodium and water secretion at 0.75 micrograms/min IA and IV, and increased hematocrit at 7.5 micrograms/min IA and and IV. Total and absorptive site blood flows and arterial and venous pressures were not changed. Intraluminal neurotensin had no effects at any infusion rate. Neurotensin can increase potassium secretion at physiologic levels by a local effect and can increase sodium and water secretion at high physiological-pathological levels through a hormonal mechanism. The secretion is not dependent on cardiovascular changes.     

Arylamino bisphosphonates: Potent and selective inhibitors of the tumor-associated carbonic anhydrase XII

A set of matrix metalloproteinases (MMPs) inhibitors, containing a bisphosphonate moiety (BP), has been evaluated for the inhibitory activity of carbonic anhydrases (CAs, EC 4.2.1.1). Human (h) isoforms hCA I, II, IX, XII and XIV were included in the study due to their involvement in crucial physiologic and pathologic processes. Some of these molecules selectively inhibited CA XII in the nanomolar range, showing an attractive dual mechanism (anti-MMP and anti-CA) of action as potential antitumor agents. The BP inhibitors investigated in this study are also excellent leads for obtaining even more effective compounds able to selectively target membrane-bound CA XII and having the potential to be used as tools for understanding physiologic processes regulated by this isoform.