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Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Pb interferes with heme biosynthesis by meddling with ferrochelatase, ALAS (δ-aminolevulinic acid synthetase), and ALAD (δ-aminolevulinic acid dehydratase) (Figure 26.7). The net effect is accumulation of protoporphyrin in RBCs and decreased formation of hemoglobin due to defective heme assembly. Clinically, patients manifest with basophilic stippling (due to accretion of polyribosomes and RNA aggregates in RBCs), which is noticeable on a Gram-stain RBC smear at 100× magnification. In addition, defective heme synthesis results in increased production of reticulocytes (immature RBCs), which is demonstrated by stippled cell cytoplasm and microcytic hypochromic anemia.
The humoral response to lung transplantation
Published in Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell, LUNG Transplantation, 2016
Glen P. Westall, Miranda A. Paraskeva, Greg I. Snell
Sudden-onset (acute) AMR might have all these features of allograft dysfunction. In the presence of other Banffstyle DSA and MFI criteria45 and additional exploration and investigation of the differential diagnosis, it is possible to make a compelling case that AMR is present and that potentially complex and expensive therapies are indicated.56 Slow-onset chronic AMR may be characterized simply by chronic dyspnea and a relatively subtle restrictive spiro-metric picture.54 As already discussed, in this situation the subsequent poor utility of lung histology and DSA assessment makes a firm diagnosis of chronic AMR essentially impossible. Figure 12.1 attempts to schematically demonstrate the different stages of AMR and their relationship to acute lung allograft dysfunction (ALAD) and CLAD “syndromes."57,58 In a significant number of cases, a firm diagnosis of chronic AMR can be made only in retrospect after a significant response to presumptive AMR therapy or after a postmortem examination or review of explant histology following retransplantation.55,59
Cutaneous Porphyrias
Published in Henry W. Lim, Herbert Hönigsmann, John L. M. Hawk, Photodermatology, 2007
Gillian M. Murphy, Karl E. Anderson
As shown in Figure 1, ADP, AIP, HCP, and VP are due to deficiencies of the second, third, sixth and seventh enzymes of the heme biosynthetic pathway. ALAD is a zinc-containing, cytosolic enzyme consisting of eight identical subunits.
Hepatotoxic effect of lead and hepatoprotective effect of Hydrilla verticillata on hepatic transcriptional and physiological response in edible fish Labeo rohita
Published in Drug and Chemical Toxicology, 2022
Pandi Prabha S., Johanna Rajkumar, Karthik C.
δ-Aminolevulinic acid dehydratase (ALAD) is a sulfhydryl containing enzyme that catalyzes the asymmetric condensation of two molecules of aminolevulinic acid (ALA-substrate) to form porphobilinogen during heme synthesis pathway. ALAD is a metalloenzyme requiring zinc ions for activity and used as a biosensor for lead poisoning (Jaffe 2000, Konuk et al.2010). Kelada et al. (2001) reported that lead displaces a zinc ion at the molecular level at the metal binding site, not the active site, producing inhibition through a change in the enzyme's quaternary structure. Administration of lead caused significant decrease in the activity of blood ALAD. Since lead has high affinity for sulfhydryl groups, this may lead to possible inhibition of ALAD activity. An inhibition in the activity of blood ALAD may lead to a significant accumulation of ALA. Therefore, there is a possibility of increased ALA to generate more reactive oxygen intermediates and thus oxidative stress. Another possible mechanism for decreased activity of ALAD may be due to toxic effect of lead in bones. Since 85% of heme syhthesis is occurring in bone marrow, the accumulation of lead in bone affects the synthesis of new blood cells, by inhibiting the enzyme ALAD involved in erythropoiesis (Yagminas and Villeneuve 1987). The reduction in red blood cell count may be due to increase in the rate of erythrocyte destruction in hematopoietic organs or due to decrease in the rate of RBC synthesis (Baranowska-Bosiacka et al.2000).
Prevalence of gestational diabetes mellitus in Argentina according to the Latin American Diabetes Association (ALAD) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria and the associated maternal-neonatal complications
Published in Health Care for Women International, 2021
Silvia Gorban de Lapertosa, Stella Sucani, Susana Salzberg, Jorge Alvariñas, Cristina Faingold, Alicia Jawerbaum, Gabriela Rovira
In this work, using the ALAD criterion, we observed an increase from a known prevalence of 5% of GDM in 1995 (Salzberg & Alvariñas, 1995) to the current prevalence of 9.8%, indicating a 2-fold increase in the GDM prevalence in the last 25 years. When comparing the GDM prevalence in the Argentine population with the ALAD and the IADPSG diagnostic criteria, it is interesting to note that the study population presented an average maternal age (27 years old) and BMI (27.3 kg/m2) similar to those observed in the population analyzed by the HAPO study (29 years old and 27.7 kg/m2, respectively) (Group – HAPO et al., 2008). In our study, the ALAD criterion led to a GDM prevalence that was markedly lower (9.8%) than the prevalence of patients diagnosed with GDM by the IADPSG diagnostic criterion (24.9%). Besides, 1.5% of the patients were diagnosed by the ALAD criterion but not by the IADPSG criterion. These women were diagnosed by glycemia values higher than 140 mg/dL in the second hour of the OGTT, suggesting a high-risk population as this glycemia value is the threshold to apply treatment.
Effect of lead exposure and nutritional iron-deficiency on immune response: A vaccine challenge study in rats
Published in Journal of Immunotoxicology, 2020
Srinivasa Reddy Yathapu, Narendra Babu Kondapalli, Sarath Babu Srivalliputturu, Rajkumar Hemalatha, Dinesh Kumar Bharatraj
A reduction in ALAD activity is considered a hallmark of subclinical Pb toxicity (Reddy et al. 2010). Here, ALAD activity in rats on the ID regimen was increased compared to that in CD rats. It is known that ALAD is a key rate-limiting enzyme in the synthesis of Hb that is regulated by already existing Hb levels in the body (Goyer and Clarkson 2001). As Fe deficiency impairs heme synthesis, and thus results in decreased physiological Hb levels, this in turn leads to increased synthesis of ALAD to meet the need for more Hb. Exposure to Pb resulted in significant reduction in ALAD activity in both control as well as Fe-deficient rats. Nevertheless, in Pb-exposed rats, the extent of reduction in ALAD activity was much higher in Fe-deficient rats (108 U) compared to in corresponding control rats (74 U). It is possible that a higher accumulation of blood Pb in the Fe-deficient rats might have augmented a reduction in Pb-mediated inhibition of ALAD activity (Table 1). The results suggest that Fe deficiency augmented Pb accumulation, leading to Pb hemotoxicities.