Biomedical subjects

J J Haddad

Publications and source records attributed to J J Haddad.

26 records · Page 2Linked to original sources

PubMed1998

Interleukin-1 beta inhibits the intestinal transport of [14C] 3-O-methylglucose in the rat.

Interleukin-1 (IL-1) is known to be a hypoglycemic cytokine, but its mechanism of action is still unknown. Since the blood glucose levels depend on the amount of glucose entering and leaving the circulation, this work was conducted to test the hypothesis that the hypoglycemia observed with IL-1beta might result, at least partially, from a reduced intestinal glucose absorption. Male Sprague Dawley rats were injected intraperitoneally (i.p.) with IL-1beta, and a jejunal segment was perfused with [14C] 3-O-methylglucose for 5, 15, 25 and 40 min. Our results showed that IL-1beta significantly inhibited the mucosal uptake of this hexose and reduced its intestinal retention. The time course and the dose response effect for this cytokine were also determined. Studies on the effect of IL-1beta on the activity of the intestinal Na+-K+ ATPase demonstrated a significant inhibition of the pump. The effect of IL-1beta on the hexose transport across the brush border membrane may thus be attributed to its inhibitory effect on the Na+-K+ ATPase.

3-O-Methylglucose↗

PubMed1998

Humoral and cell-mediated immunopotentiation in vaccinated chicken layers by thymic hormones and zinc.

The humoral and cell-mediated immunities to a trivalent killed vaccine, administered subcutaneously to white leghorn-chicken layers at 29 and 31 weeks of age, and containing antigens of infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and Newcastle disease virus (NDV), were quantitated in five vaccinated and one unvaccinated-control group. Four out of the five vaccinated groups were immunopotentiated by various combinations of zinc and thymic hormones administered intraperitoneally in a volume of 0.1 ml per bird at an interval of three days for a period of three weeks, starting at 29 weeks of age. At each time interval, each bird of the first group received thymulin (10 ng) and ZnCl2 (1 microM), while each bird of the second group received thymopoietin (25 ng) and ZnCl2 (1 microM); in the third group, each bird received thymulin (10 ng), thymopoietin (25 ng), and ZnCl2 (1 microM), while each bird of the fourth group received only ZnCl2 (1 microM). Birds of the fifth group were only vaccinated and the control birds in the sixth group were left without vaccination or other immunopotentiation. Among all combinations, the thymulin-ZnCl2 resulted in birds with the highest humoral immunopotentiation to IBV, IBDV, and NDV antigens with respective percent increase in the mean titer at 33 weeks of age, compared with initial titer at 29 weeks of age, equivalent to 199%, 671.7%, and 86.4%. The highest cell-mediated delayed hypersensitivity reaction, measured at 48 h following an intradermal administration of the trivalent vaccine in the wattles at 33 weeks of age, was obtained in chickens immunopotentiated by the thymulin-thymopoietin-ZnCl2 combination.

Adjuvants, Immunologic↗

PubMed1997

Involvement of interleukin-1 beta, nerve growth factor and prostaglandin E2 in endotoxin-induced localized inflammatory hyperalgesia.

1. Intraplantar endotoxin (ET) injection (1.25 micrograms) into the hind paw of rats resulted in a localized inflammatory hyperalgesia, as assessed by paw pressure (PP), paw immersion (PI), tail flick (TF) and hot plate (HP) tests. 2. ET injection resulted in a significant elevation in the levels of interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) in the injected foot as compared with the non-injected foot. This increase was attenuated by intraperitoneal injections of dexamethasone (200 and 400 micrograms kg-1) and to a lesser extent by indomethacin (2 and 8 mg kg-1). 3. The tripeptide Lys-D-Pro-Val, which is known to antagonize IL-1 beta and prostaglandin E2 (PGE2) reversed mechanical hyperalgesia, as assessed by the PP test, and reduced significantly thermal hyperalgesia, as assessed by the HP and TF tests. 4. IL-1ra reversed both mechanical (PP) and thermal (PI) nociceptive thresholds tested on the injected leg and significantly reduced thermal hyperalgesia, as assessed by the HP and TF tests. 5. A sheep, anti-mouse NGF antiserum reversed mechanical hyperalgesia (PP test) but had little or no effect on thermal hyperalgesia (PI, HP and TF tests). 6. Our results indicate the importance of IL-1 beta, NGF and prostaglandin E2 (PGE2) in the development of ET induced hyperalgesia and the possible existence of different mechanisms underlying thermal and mechanical as well as central and peripheral hyperalgesia.

Animals↗

PubMed1997

Effects of various analgesic and anti-inflammatory drugs on endotoxin-induced hyperalgesia in rats and mice.

A new model of endotoxin (ET)-induced hyperalgesia has been used to test the effects of four classes of drugs in rats and mice. Hyperalgesia was assessed by paw pressure (PP), hot plate (HP) and tail flick (TF) tests. Each drug was injected intraperitoneally 24 and 12 h before ET injection and just before each pain test at 3, 6, 9 and 24 h after ET injection. At the dosages used, acetaminophen and dexamethasone were the most effective in reducing PP hyperalgesia and least effective on TF hyperalgesia, while indometacin and morphine produced their main effect on TF hyperalgesia. The four drugs were about equally effective in reversing HP hyperalgesia. We conclude that ET hyperalgesia is mediated by both prostaglandin-sensitive and prostaglandin-independent mechanisms.

Acetaminophen↗

PubMed1996

Thymulin reduces hyperalgesia induced by peripheral endotoxin injection in rats and mice.

In a new model of peripheral localized inflammation, induced by intraplantar endotoxin (1.25 micrograms) injection in the hind paw of rats and mice, thymulin, a hormone of the thymus gland involved in immunomodulation, reduced inflammatory pain. High doses of thymulin reduced significantly, and in a dose-dependent manner, mechanical hyperalgesia as assessed by the paw pressure test and thermal hyperalgesia as assessed by the hot plate test and tail immersion test.

Animals↗

PubMed1996

Endotoxin-induced local inflammation and hyperalgesia in rats and mice: a new model for inflammatory pain.

Lipopolysaccharide, also known as endotoxin (ET), is a major constituent of the outer membrane of the cell wall of most gram negative bacteria. ET is known to cause a number of pathophysiological changes associated with illness including inflammatory pain. The aim of this study is to characterize the peripheral hyperalgesia induced by ET in rats and mice. Different groups of rats and mice received different doses of ET ranging from 0.6 microgram to 40 micrograms dissolved in 50 microliters saline and injected in the plantar area of the left hind legs. All animals were subjected to tail immersion (TF), hot plate (HP) and paw pressure (PP) tests, 2-3 days prior to ET injection and during the following 1-2 days. ET injections produced a dose-dependent decrease in the latencies of the HP and PP tests of the injected leg reaching a maximum decrease of 50-60% of the control with 20-40 micrograms ET at 9 h (rats) and 24 h (mice) after the injection. Almost complete recovery was observed after 24 h in rats and 48 h in mice. TF latencies showed a less but a significant decrease while PP of the opposite leg and all tests in saline-injected animals did not elicit significant variations and served as additional controls. Our results indicate that the use of ET-produced hyperalgesia is a valid model for local and reversible inflammatory pain, with minimal distress to the animal. This model can also be used to study the efficacy of various anti-inflammatory and analgesic drugs and the molecular mechanisms of inflammation induced by bacterial invasion.

Animals↗

PubMedDate not supplied

Calcium homeostasis during therapeutic plasma exchange.

Because the removal of substantial quantities of plasma calcium during plasma exchange is rarely attended by clinically significant hypocalcemia, we evaluated calcium homeostasis during this procedure. Twenty-one procedures were performed on 10 patients with various neurological disorders. The reduction by plasma exchange in the serum concentrations of total calcium, ionized calcium, magnesium, and phosphate was significantly less than predicted (p less than 0.001) based on plasma volume of the patient and size of the exchange. However, N-terminal parathomone (PTH) levels increased to 242 +/- 120 percent midway into the procedure and were 207 +/- 84 percent after plasma exchange; urinary cyclic adenosine monophosphate (cAMP) levels rose by 165 +/- 35 percent. These data demonstrate a rapid compensatory response in N-terminal PTH and urinary cAMP to the reduction by plasma exchange of serum concentrations of total calcium, ionized calcium, and phosphate. The routine administration of supplemental calcium during plasma exchange may therefore be unnecessary in patients with normal parathyroid function.

Adrenal Cortex Hormones↗

PubMedDate not supplied

L-Buthionine-(S,R)-sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, augments LPS-mediated pro-inflammatory cytokine biosynthesis: evidence for the implication of an IkappaB-alpha/NF-kappaB insensitive pathway.

The pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, contribute to the exacerbation of pathophysiological conditions in the lung. The regulation of cytokines involves the reduction-oxidation (redox)-sensitive nuclear factor-kappaB (NF-kappaB), the activation of which is mediated through an upstream kinase that regulates the phosphorylation and subsequent degradation of inhibitory-kappaB (IkappaB)-alpha, the major cytosolic inhibitor of NF-kappaB. It was hypothesized that lipopolysaccharide (LPS)-induced biosynthesis of TNF-alpha and IL-6 in vitro is tightly regulated by redox equilibrium. Furthermore, the likely involvement of the IkappaB-alpha/NF-kappaB signalling transduction pathway in mediating redox-dependent regulation of LPS-induced cytokine biosynthesis was revealed. Using alveolar epithelial cells, the role of L-buthionine-(S,R)-sulfoximine (BSO), a specific and irreversible inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in glutathione (GSH - an antioxidant thiol) biosynthesis, in regulating LPS-mediated TNF-alpha and IL-6 production and the IkappaB-alpha/NF-kappaB signalling pathway was investigated. Pre-treatment with BSO, prior to exposure to LPS augmented, in a dose-dependent manner, LPS-induced TNF-alpha and IL-6 biosynthesis, an effect associated with the induction of intracellular accumulation of reactive oxygen species (ROS). Interestingly, BSO blocked the phosphorylation of IkappaB-alpha, reduced its degradation, thereby allowing its cytosolic accumulation, and subsequently inhibited the activation of NF-kappaB. These results indicate that there are ROS and redox-mediated effects regulating pro-inflammatory cytokines, and that the IkappaB-alpha/NF-kappaB pathway is redox-sensitive and differentially involved in mediating redox-dependent regulation of cytokine signaling.

Animals↗