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Biomedical subjects

M Badr

Publications and source records attributed to M Badr.

At least 37 records · Page 2Linked to original sources

Carbohydrate and oxygen metabolism during hepatocellular proliferation: a study in perfused livers from mirex-treated rats.

Liver regeneration after partial hepatectomy is accompanied by altered hepatic intermediary metabolism. Because the organochlorine compound mirex also causes liver cell growth, the purpose of this study was to investigate hepatic carbohydrate and oxygen metabolism in perfused livers from mirex-treated rats and to localize cell proliferation in this model. Pretreatment with mirex (100 mg/kg, intragastrically) increased liver/body weight ratios and DNA synthesis in livers of fed rats, effects that were markedly diminished in livers of fasted rats. This finding shows that liver growth caused by mirex, as is the case after partial hepatectomy, is hindered when animals are deprived of food. Furthermore, perfused livers from mirex-treated rats had depleted glycogen stores but significantly elevated oxygen uptake compared with livers from control rats. Increases in oxygen uptake and hepatocellular proliferation were observed mostly in periportal regions of the liver lobule. In regenerating livers, most DNA synthesis was reported to also occur in these regions of the liver lobule. Taken together, these data show that liver cell growth caused by mirex is accompanied by changes in hepatic intermediary metabolism and sublobular proliferation similar to those observed after partial hepatectomy.

Animals↗

Mechanism of aluminum-induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase.

Aluminum, an abundant element in the earth's crust, has been implicated in various pathological disorders and low concentrations of this element have recently been shown to inhibit brain glycolysis. However, despite the fact that aluminum accumulates in high concentrations in the liver, potential effects of this metal on hepatic intermediary metabolism have not been explored. In perfused livers from untreated rats, maximal rates of production of lactate plus pyruvate (glycolysis) were 93 +/- 15 mumols/g/hr. Glycolysis was severely inhibited in livers from aluminum-treated rats (0.5 mg/kg, 6 hr before experiment) with maximal rates of only 23 +/- 4 mumols/g/hr. In contrast, glucose production (glycogenolysis) and hepatic oxygen uptake were not altered significantly by prior treatment with aluminum. In livers from fasted rats, pretreatment with aluminum did not influence gluconeogenesis or production of lactate and pyruvate from fructose (5 mM). This finding indicates that pyruvate kinase is not inhibited by aluminum and implicates phosphofructokinase, hexokinase and/or glucokinase as sites for the inhibitory effect of aluminum on glycolysis. In liver homogenates from untreated rats, increasing concentrations of aluminum did not show any appreciable effect on hexokinase or glucokinase activity but did cause progressive decreases in phosphofructokinase activity. Therefore, aluminum-induced inhibition of liver phosphofructokinase, an important control site in the glycolytic pathway, is most likely responsible for aluminum-induced inhibition of hepatic glycolysis.

Adenosine Triphosphate↗

Changes in hippocampal LH-RH receptor density during maturation and aging in the rat.

In earlier studies, we have reported the presence of luteinizing hormone-releasing hormone (LH-RH) binding sites in different rat brain areas including the hippocampus, lateral septum, amygdaloid nucleus and subiculum. We have also demonstrated that sex steroids can modulate the concentrations of brain LH-RH receptors. The role of hormonal status during different stages of development in regulating hippocampal LH-RH receptor concentration was assessed using in vitro autoradiography performed on slide-mounted frozen sections. Labeling was measured quantitatively by optical densitometry. Female and male rats of different ages (from birth to 21 months of age) were used in these experiments. The results obtained were similar in both sexes. As early as 6 days of age, LH-RH binding sites could be detected. The concentration of receptors increased with time and reached a maximum at 35 and 45 days of age for male and female, respectively. Thereafter, the receptor concentrations decreased and were at their minimum in middle-age animals. In older rats (17 and 21 months of age), LH-RH binding sites increased in concentration. These results suggest that, at the time of puberty, hormonal status induces an increase in the density of brain LH-RH receptors whilst in older rats, as previously demonstrated in castrated animals, the decreased production of gonadal hormones results in an increase in receptor concentration.

Aging↗

Effect of verapamil on glycogenolysis and gluconeogenesis in the perfused rat liver.

In perfused livers from fed rats, rates of glucose production (glycogenolysis) were 133 +/- 12 mumol/g/hr. Infusion of 2 microM verapamil into these livers decreased the rates of glucose production significantly to 97 +/- 15 mumol/g/hr within 10 min. Conversely, rates of production of lactate plus pyruvate (glycolysis) of 64 +/- 6 mumol/g/hr were not significantly altered by verapamil (60 +/- 3 mumol/g/hr). When 50 microM verapamil was infused, however, rates of both glycogenolysis and glycolysis were diminished to 56 +/- 11 and 43 +/- 5 mumol/g/hr, respectively. In perfused livers from fasted rats, infusion of 20 mM fructose increased the rates of production of glucose (gluconeogenesis) significantly from 11 +/- 7 to 121 +/- 17 mumol/g/hr. These rates reached 138 +/- 7 mumol/g/hr upon the simultaneous infusion of verapamil (2 microM). In these livers, fructose also increased rates of production of lactate from 6 +/- 2 to 132 +/- 11 mumol/g/hr, which were further increased to 143 +/- 8 mumol/g/hr when 2 microM verapamil was infused. The results show that calcium-dependent processes involved in hepatic carbohydrate metabolism respond differently to the calcium channel blocker verapamil. Low concentrations of verapamil inhibited glycogenolysis significantly while having no effect on either glycolysis or gluconeogenesis. These data suggest that these two processes have different sensitivities to changes in intracellular calcium concentrations and/or different sources of regulatory calcium.

Animals↗

Use of slide-mounted frozen sections to study the autoradiographic localization, characterization and quantification of luteinizing hormone-releasing hormone receptors in the rat pituitary.

Slide-mounted frozen sections were used for the autoradiographic localization, characterization and quantification of LHRH receptors. The radioligand was the iodinated LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A). Specificity studies demonstrated that specific labeling was concentrated in the anterior pituitary lobe and that the tracer could be displaced with either LHRH or LHRH-A. Scatchard analysis of saturation curves gave one-site interactions with a high affinity (Kd = 0.48 +/- 0.1 nM) for the iodinated LHRH-A. In order to evaluate the effects of different treatments on the LHRH receptor concentration, the effects of sex steroids on the density of radioautographic reaction were evaluated using an image analyzer. The results obtained were similar to those previously reported with classical binding assays. Thus, this simple technique appears suitable for the study of localization and characterization of LHRH receptors in different experimental conditions.

Animals↗

High resolution autoradiographic localization of LHRH receptors in the rat anterior pituitary using fixed sections.

The cellular and subcellular localization of luteinizing hormone-releasing hormone (LHRH) receptors in rat anterior pituitary has been studied at the light and electron microscopic levels using in vitro autoradiography performed on fixed pituitary sections. The iodinated LHRH agonist [D-Ser(TBU)6,des-Gly-NH10(2)]LHRH ethylamide was used as the ligand. In semithin sections of pituitaries from castrated rats, specific labeling was exclusively localized over the castration cells. At the ultrastructural level, the analysis of silver grain distribution performed in gonadotrophs revealed that the plasma membrane, rough endoplasmic reticulum, and Golgi apparatus were significantly labeled. These findings are consistent with previous reports indicating the presence of specific LHRH binding sites in the plasma membrane. This is also the first demonstration that LHRH receptors are associated with intracytoplasmic organelles. Moreover, this ultrastructural technique should be very useful to localize with precision LHRH receptors in other organs, especially the brain.

Animals↗

Characterization and autoradiographic localization of LHRH receptors in the rat brain.

Luteinizing-hormone-releasing hormone (LHRH) is distributed in several extrahypothalamic areas, suggesting that it might act as a neurotransmitter or neuromodulator in the central nervous system. This study was undertaken to characterize and localize LHRH receptors in the rat brain by using slide-mounted frozen sections. The radioligand used was an iodinated stable LHRH agonist, [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide. It was clearly established that LHRH receptors with characteristics similar to those of pituitary LHRH receptors were present in the brain. They were found in high concentrations in the dorsal hippocampus, amygdala, septum, and subiculum and in very low amounts in the hypothalamus. Generally, a good correlation could be observed between receptor distribution and immunohistologically localized LHRH. These results strongly suggest that LHRH has multiple sites of action in the rat brain and reinforce the hypothesis that the peptide could act as a neurotransmitter/neuromodulator in the central nervous system.

Animals↗

Menadione causes selective toxicity to periportal regions of the liver lobule.

Infusion of increasing concentrations (0.2-1 mM) of the quinone, menadione, caused step-wise increases in oxygen uptake in perfused livers from fasted rats presumably due to oxygen-dependent redox cycling. Maximal increases in oxygen uptake of about 40 mumol/g/h were observed with 0.8 to 1.0 mM menadione. This increase in oxygen uptake was confined to periportal areas of the liver lobule suggesting that redox cycling due to menadione occurs exclusively in cells localized around the portal triad. After 60 min of infusion of menadione (1 mM), lactate dehydrogenase was released from the liver at rates between 60 to 70 U/g/h. Under these conditions, trypan blue was taken up by virtually all hepatocytes in periportal regions of the liver lobule. In contrast, dye was not taken up by cells in pericentral areas. It is concluded that menadione is selectively toxic to hepatocytes located in oxygen-rich periportal regions of the liver lobule.

Animals↗

Ovarian adrenergic nerves directly participate in the control of luteinizing hormone-releasing hormone and beta-adrenergic receptors during puberty: a biochemical and autoradiographic study.

The rat ovary receives sympathetic innervation from the superior ovarian nerve (SON) and the plexus nerve (OP). To examine the possibility of a direct adrenergic mechanism controlling ovarian receptor distribution during the onset of puberty, we have studied the acute (48-h) effect of unilateral nervotomy (combined section of SON and OP nerves) on ovarian LHRH and beta-adrenergic receptor concentrations and distribution using both radioreceptor assays and in vitro autoradiography. Ovarian LHRH receptor concentration increased sharply between 12 and 20 days of age. At this time receptors were mostly associated with follicles and interstitial cells, whereas at 37 days of age, when a measurable loss in the receptor concentration was observed, light and diffuse autoradiographic labeling of receptors was also found in the corpora lutea. Complete removal of adrenergic input to the gland produced a sharp decrease in LHRH-binding activity within the denervated ovary at each time interval studied, with no effect in the innervated contralateral gland. Autoradiographic data also revealed a decrease in both the number of labeled follicles and the intensity of the labeling. beta-Adrenergic receptor concentration increased progressively between days 12 and 27, reaching a peak value at 37 days of age. Labeling was very weak at 12 days of age and increased progressively at 20 and 27 days of age. At this time, receptors were mostly localized by autoradiography in the interstitial cells, while at 37 days of age corpora lutea were strongly labeled. Ovarian beta-adrenergic receptors showed a marked drop when acutely deprived of their neural tone, as illustrated by the 2- to 3-fold decrease in receptor-binding capacity within the denervated gland. The autoradiographic data also showed marked changes in beta-adrenergic receptor distribution, specially at 37 days of age. At this time, the labeling of corpora lutea was markedly decreased in denervated ovaries. The present results clearly demonstrate that complete removal of ovarian adrenergic tone produces a profound decrease in the concentrations of LHRH and beta-adrenergic receptors within the ovary, although it cannot be excluded that peptidergic factors also arriving via the SON and OP could have some influence on the regulation of these receptors. The results support the concept of a direct involvement of the central nervous system in ovarian function. They also suggest that during ovarian development a neural efferent system might be involved in the adjustment of ovarian responsiveness to stimulation by the gonadotropins via changes in receptor content and/or distribution in the different ovarian compartments.

Animals↗

Partial flap ureteroneocystostomy for bilharzial strictures of lower ureter.

Partial flap ureteroneocystostomy was applied for the management of bilharzial strictures of the lower ureter for 30 ureters (24 patients). Follow-up excretory urography (IVP) showed improvement or stabilization in 83.3 per cent of renoureteral units. Creatinine clearance improved or remained stable in 79 per cent of cases. Postoperative reflux occurred in 30 per cent of renoureteral units. We recommend partial flap ureteroneocystostomy for the management of bilharzial strictures if submucosal tunnel ureteroneocystostomy is not applicable.

Adult↗

Management of bilharzial strictures of the lower ureter.

Ureteral strictures are serious and frequent complications of chronic bilharziasis of the urinary tract are seen. To determine which corrective surgical procedures are most successful, we compared the results of those most commonly done. We retrospectively analyzed our experience with mucosa to mucosa ureterovesical anastomosis (68 ureters), transvesical ureteral meatotomy (30 ureters) are submucosal tunnel ureteroneocystostomy, (UNC; 10 ureters). Complete follow-up data are available for 102 patients (108 ureters); half of these cases were followed for 4 years or even more. It is to be noted that, in our series, only 10 ureters were suitable for submucosal tunnel anastomosis: bilharzial ureters are usually fibrotic, noncompressible, and the vesical mucosa is adherent to the muscular layer - which renders creation of a tunnel difficult or impossible. However, this procedure produced the best results. The conclusion was reached that, whenever possible, antireflux procedures suitable for the bilharzial bladder and ureter should be attempted. Based on this analysis, a prospective clinical trial was carried out, which compared Boari flap UNC (30 ureters), triangular flap ureterovesicoplasty of Girgis et al. (30 ureters), and ileal loop replacement of the pathologic segment (30 ureters). The average period of follow-up was 20 months. Triangular flap and Boari flap were found to be superior to ileal replacement. Ileal replacement is consistently followed by vesicoileal reflux and commonly by persistent urinary tract infection. In consequence, the latter operation must be reserved for cases with extensive ureteral loss or destruction. Antireflux procedures still remain the most desirable methods whenever technically possible.

Adult↗