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P Haddad

Publications and source records attributed to P Haddad.

65 records · Page 4Linked to original sources
PubMed1986

Influence of calcium or 1,25-dihydroxyvitamin D3 supplementation on the hepatic microsomal and in vivo metabolism of vitamin D3 in vitamin D-depleted rats.

Hypocalcemic vitamin D (D)-depleted rats were supplemented with calcium or 1,25(OH)2D3, and the metabolism of D3 to 25(OH)D3 was studied. Infusion with 7 or 65 pmol 1,25(OH)2D3 X 24 h-1 led to normal or slight hypercalcemia associated with physiological and supraphysiological plasma concentrations of the hormone while calcium supplementation normalized plasma calcium despite 1,25(OH)2D3 concentrations as low as those observed in hypocalcemic controls. Constant administrations of [14C]D3 during the supplementation regimens uncovered a stimulation of the in vivo 25(OH)D3 production by calcium supplementation; this was further confirmed in vitro by an increase in the hepatic microsomal D3-25 hydroxylase. The group supplemented with pharmacological doses of the hormone displayed lower circulating concentrations of both D3 and 25(OH)D3 while the in vitro 25(OH)D3 production remained unaffected by 1,25(OH)2D3. Investigation of the kinetics of intravenous 25(OH)[3H]D3 revealed similar elimination constants in all groups. The data indicate that calcium supplementation of hypocalcemic D-depleted rats results in an increased transformation of D3 into 25(OH)D3 while supplementation with 1,25(OH)2D3 does not affect the in vitro D3-25 hydroxylase but seems to influence the in vivo handling of the vitamin by accelerating its metabolism.

Animals↗
PubMed1985

Microsomal C-25 hydroxylation of [3H]-vitamin D3 by the fetal and neonatal rat liver.

The liver microsomal C-25 hydroxylation of [3H]-vitamin D3 was evaluated in 19- and 22-day-old rat fetuses, and in 1-, 2-, 3-, 14-, 30-, and 60-day-old pups. The hepatic production of [3H]-25-hydroxyvitamin D3 by the 19- and 22-day-old fetuses was evaluated at 2.3 +/- 0.6 and 5.9 +/- 0.6 fmol . min-1 . 15 mg-1 microsomal protein, respectively. Values stayed unchanged during the 1st day after birth but increased on days 2 and 3 of chronologic age. Thereafter, the activity remained at a plateau of 11.2 +/- 0.6 fmol . min-1 . 15 mg-1 microsomal protein with no further statistically significant increase in the activity of the vitamin D3-25 hydroxylase through 60 days of chronologic age. The microsomal cytochrome P-450 specific content increased during the perinatal period with values ranging from 0.15 nmol . mg protein-1 in 22-day-old fetuses to 0.44 in 60-day-old rats; the developmental pattern of the cytochrome P-450 was similar to that observed for the vitamin D3-25 hydroxylase activity. When the amount of [3H]-25-hydroxyvitamin D3 formed was expressed in relation to the amount of enzyme present in the reaction medium, a constant C-25 hydroxylation capacity in all age groups was observed suggesting that the cytochrome P-450 isoenzyme responsible for the C-25 hydroxylation of vitamin D3 may be constitutionally determined and that its appearance originates during fetal life.

Age Factors↗
PubMed1985

Comparative hepatic response to bromobenzene and allyl alcohol in the vitamin D-replete and vitamin D-depleted rat.

Vitamin D-depleted and vitamin D-replete rats were treated with allyl alcohol (AA) or bromobenzene (BB). The severity of the hepatotoxicity was evaluated by the serum concentrations of aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase, the histomorphological appearance of the lesions, and the amount of cytochrome P-450 destroyed. The activity of the monooxygenases was also evaluated. All parameters indicated that vitamin D depletion alone did not lead to any signs of liver toxicity nor did it modify the pattern of toxicity of either AA or BB. However, the intensity of the response in the periportal (AA treatment) and in the centrilobular (BB treatment) zones was modified by the depletion. Vitamin D depletion was accompanied by increased hepatic damage due to AA while BB resulted in less hepatic damage in vitamin D-depleted compared to vitamin D-replete animals. The metabolic profile of the liver mixed function oxidases indicated that its intraacinar distribution was modified by the depletion. Although the overall activity toward the substrates studied was not changed by vitamin D depletion, two out of the three enzyme activities studied suggested that vitamin D-depleted rats were poorer "centrilobular metabolizers" and better "periportal metabolizers" than vitamin D-replete rats. These observations correspond to increased periportal and decreased centrilobular toxicity in vitamin D-depleted animals. These results suggest that vitamin D depletion associated with severe hypocalcemia may be associated with an intraacinar modulation of enzyme systems as well as with an intraacinar difference in the susceptibility of the liver to certain chemicals.

1-Propanol↗
PubMed1976

Lymphoma of the spinal extradural space.

Ninety-four patients with lymphoma involving the extradural space with spinal cord compression proven at the time of laminectomy were reviewed. There were about three times as many patients with non-Hodgkin's lymphoma than with Hodgkin's disease. The majority of those with Hodgkin's disease had a proven histologic diagnosis before the onset of the spinal cord compression syndrome, whereas only 15% of those with non-Hodgkin's lymphoma had previously been so diagnosed. Plain roentgenograms of the spine were suggestive of tumor involvement in less than one-third of the patients, whereas myelograms were invariably abnormal. As noted by others, the outlook for functional recovery and extended life expectancy is relatively good for patients with this type of cancer, in contrast to reports in the literature regarding prognosis for patients who have metastatic carcinoma with extradural spinal cord compression.

Adolescent↗
PubMedDate not supplied

Involvement of granzyme B and perforin gene expression in the lytic potential of human natural killer cells.

Natural killer (NK) cells (CD3-) or large granular lymphocytes (LGL) spontaneously kill K562 targets but are unable to kill Daudi cells in the absence of IL-2 stimulation. IL-4 is reported to prevent or inhibit the IL-2-driven lymphokine-activated killer (LAK) generation in NK cells. Therefore, we wished to determine whether the antagonistic effect of IL-4 on IL-2-induced LAK activity might regulate the expression of genes encoding proteins involved in lysis, such as perforin, the pore-forming protein, or which are associated with lysis, such as granzymes A and B. By using in situ hybridization, we showed that, in addition to inducing LAK activity, IL-2 stimulation increased the amount of perforin and granzyme B mRNA at the single-cell level in 40 to 100% of the total CD3- LGL cell population. In addition, our results indicated that the stimulatory effect of IL-2 can be downregulated by IL-4 for both LAK activity and granzyme B and perforin gene expression. Here again, a decrease in the amount of specific mRNA per cell was noted. These findings suggest that modulation of the lytic machinery via lymphokines might be associated with regulation of the lytic potential of NK cells.

Cytotoxicity, Immunologic↗
PubMedDate not supplied

Implementing an effective intervention for problem drinkers on medical wards.

Many medical inpatients have alcohol related problems but evidence of the feasibility of instituting a brief intervention is incomplete. An alcohol counsellor trained nurses on five general medical wards to screen patients routinely for alcohol problems. She counselled appropriate patients using one or two counselling sessions. Efficacy of the counselling was assessed at interview six months following the admission. We found that 19.6% of male and 4.8% of female medical patients were drinking more than 50 units (U) or 33 drinks per week (male) or 35 U or 23 drinks per week (female). Counselling, with one or two sessions led to a reduction from a median of 74 U (49 drinks) per week at admission to 26 U (17 drinks) per week at six months follow-up. A second counselling session after discharge showed no advantage over a single one administered while the patient was in the ward. The barriers to developing a successful alcohol screening and counselling service in medical wards can be overcome provided there is also adequate support and training of the ward nursing staff.

Adult↗
PubMedDate not supplied

Cell volume regulation in liver.

The maintenance of liver cell volume in isotonic extracellular fluid requires the continuous supply of energy: sodium is extruded in exchange for potassium by the sodium/potassium ATPase, conductive potassium efflux creates a cell-negative membrane potential, which expelles chloride through conductive pathways. Thus, the various organic substances accumulated within the cell are osmotically counterbalanced in large part by the large difference of chloride concentration across the cell membrane. Impairment of energy supply leads to dissipation of ion gradients, depolarization and cell swelling. However, even in the presence of ouabain the liver cell can extrude ions by furosemide-sensitive transport in intracellular vesicles and subsequent exocytosis. In isotonic extracellular fluid cell swelling may follow an increase in extracellular potassium concentration, which impairs potassium efflux and depolarizes the cell membrane leading to chloride accumulation. Replacement of extracellular chloride with impermeable anions leads to cell shrinkage. During excessive sodium-coupled entry of amino acids and subsequent stimulation of sodium/potassium-ATPase by increase in intracellular sodium activity, an increase in cell volume is blunted by activation of potassium channels, which maintain cell membrane potential and allow for loss of cellular potassium. Cell swelling induced by exposure of liver cells to hypotonic extracellular fluid is followed by regulatory volume decrease (RVD), cell shrinkage induced by reexposure to isotonic perfusate is followed by regulatory volume increase (RVI). Available evidence suggests that RVD is accomplished by activation of potassium channels, hyperpolarization and subsequent extrusion of chloride along with potassium, and that RVI depends on the activation of sodium hydrogen ion exchange with subsequent activation of sodium/potassium-ATPase leading to the respective accumulation of potassium and bicarbonate. In addition, exposure of liver to anisotonic perfusates alters glycogen degradation, glycolysis and probably urea formation, which are enhanced by exposure to hypertonic perfusates and depressed by hypotonic perfusates.

Animals↗
PubMedDate not supplied

Comparative effects of UW and SLS solutions on concentrative proline uptake in cold preserved rat hepatocytes.

In previous studies, we have shown that the rate of cell swelling induced by concentrative proline uptake in isolated rat hepatocytes decreased by 50 per cent after only 24 h of cold storage in University of Wisconsin (UW) solution, thereby representing a sensitive marker of alterations in hepatocyte functions after cold preservation and rewarming. We have thus used concentrative proline uptake to compare the capacity of UW and sodium-lactobionate-sucrose (SLS) solutions to maintain such differentiated hepatocyte functions. Isolated rat hepatocytes were kept at 4 degrees C for 4, 10, 24 and 48 h in UW or SLS solutions, and subsequently cultured at 37 degrees C for 1-2 h. Viability was measured by Trypan blue exclusion. After rewarming, cells were subjected to a 10 min administration of 10 mM proline and accumulation of the amino acid was assessed by changes in cell volume as measured by digital analysis of single-cell images obtained under bright-field illumination. Cell viability was reduced gradually and significantly after 0 to 48 h of preservation, and rewarming amplified this effect. However, loss of viability was similar in UW- and SLS-stored cells, as were initial steady-state cell volumes. Proline-induced swelling rate was reduced significantly by 13, 46 and by 57 per cent after 10, 24 and 48 h of preservation in UW solution, respectively. There is no significant difference between SLS- and UW-preserved hepatocyte swelling rates after 10 h and 48 h of cold preservation. However, the decline in the swelling rate of SLS-preserved hepatocytes incubated for 24 h is significantly lower than that of their UW-preserved counterparts. These results show that the SLS solution can preserve differentiated hepatic functions as well as the UW solution does.

Adenosine↗