To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.
© 2011 John Wiley & Sons A/S.

INTRODUCTION: Heme oxygenase (HO) enzyme catalyzes the rate limiting step in oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO has been shown to share many properties with nitric oxide (NO), including activation of guanyl cyclase, signal transduction, and gene regulation.

AIM: To assess the signaling pathways mediating cavernous tissues response to sildenafil citrate intake experimentally.

MAIN OUTCOME MEASURES: In dissected cavernous tissues; detection of HO-1, HO-2 and nueronal nitric oxide synthase (nNOS) gene expressions by reverse transcriptase polymerase chain reaction (RT-PCR), HO enzyme activity assay, HO-1, HO-2 protein detection by Western blot, cyclic guanosine monophosphate (cGMP) tissue levels by enzyme linked immunosorbent assay (ELISA) and histopathology.

METHODS: Two hundred forty Sprague-Dawley rats divided into five equal groups were investigated: group (Gr) 1, controls received regular diet; Gr 2, received sildenafil citrate 4 mg/kg orally; Gr 3, received the same dose of sildenafil added to HO inducer, diferuloylmethane; Gr 4, received sildenafil added to HO inhibitor, zinc protoporphyrin, and Gr 5, received sildenafil kg orally by gastric tube. Gr 3 received the same dose of sildenafil added to HO inducer, added to nitric oxide synthase inhibitor, L-Nitroarginine methylester. Twelve rats from each group were sacrificed by cervical dislocation successively after 1/2, 1, 2, and 3 hours from the intake.

RESULTS: HO-2 gene expression was demonstrated in all groups. HO-1 was not expressed in controls, expressed in Gr 2, accentuated in Gr 3, and attenuated in Gr 4 and 5. These results were confirmed by Western blot. The nNOS was expressed in controls, increased in Gr 2 and 3, and decreased in Gr 4 and 5. HO enzyme activity and cGMP levels were significantly elevated in Gr 2, accentuated in Gr 3, and significantly decreased in Gr 4 and 5 compared to controls. Vasodilatations were observed in cavernous tissues of histopathologic sections of Gr 2 and increased in those of Gr 3.

CONCLUSION: Sildenafil citrate actions may be mediated by up-regulation of HO-1 gene expression.

Psoriasis is an autoimmune skin disease characterized by hyperproliferation of keratinocytes due to interplay between keratinocytes and immune cells. Iron status plays an important role in modifying the function of the immune system. Heme oxygenase (HO), heme-degrading enzyme, plays important role in protective response to oxidative cellular stress. We aimed in this study to map the iron status and HO levels and declare the role HO enzyme in iron homeostasis and immune-modulation in psoriasis. Fifty-one patients with psoriasis and 50 age- and sex-matched healthy controls were enrolled in this study. 5 mL blood sample was withdrawn from each subject. Hepcidin, iron soluble transferring receptor (sTfR), and total iron binding capacity (TIBC) were estimated using ELISA technique and, HO-1 gene level was detected using RT-PCR (reverse transcription-polymerase chain reaction). Iron levels, TIBC, and hepcidin were significantly lower in cases compared to controls. On the contrary, sTfR and HO-1 were significantly over-expressed in cases compared to controls (p < 0.05 in all). HO-1 expression negatively correlated with PASI score and disease extent (%) (r = - 0.614-, p = 0.001; r = - 0.807-, p = 0.001 respectively). There were no significant associations between HO-1 expression and iron, TIBC, hepcidin, sTfR levels (p > 0.05 in all). Iron supplements for the patients with psoriasis are important to maintain haematopoiesis. The induction of HO-1 might have be a promising approach for the treatment of psoriasis through antioxidant ability, immunomodulatory role as well as its role in heme synthesis.

Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, HSCT requires tremendous resources, and it is increasingly challenging for transplantation experts to practice in the developing world and to reach a compromise between requirements and available resources. Based on 30 years of experience and 4256 transplants (60% allogeneic and 40% autologous), this article focuses on the challenges our HSCT program encountered since it started in 1989 and what opportunities we see to solve them. Since 1997, HSCT procedures increased dramatically with the opening of 15 HSCT units distributed all over Egypt.

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Hematopoietic SCT is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 18 years of experience and more than 1300 transplants, this article will focus on special issues, which we think are important for hematopoietic SCT practices in developing countries, taking the program in Egypt as an example that may be applicable to other countries in the developing world. The SCT program in Egypt started in 1989 on a narrow scale. In 1997, the transplant rate increased dramatically with the opening of the SCT unit at the Nasser Institute. Our team is registered in the Center for International Blood and Marrow Transplant Research. The total number of transplants performed till June 2007 is 1362; 80% of the cases are allogeneic and 20% autologous. There are seven other centers in Egypt performing mainly autologous transplants.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used for high-risk acute lymphoblastic leukemia (ALL) patients in their first complete remission (CR1), and for relapsed patients in second complete remission (CR2).

PATIENTS AND METHODS: We retrospectively analyzed data for 67 children with ALL, from a cancer center in a low/middle income country, who had undergone HSCT from human leukocyte antigen (HLA)-matched sibling donors (MSDs) using myeloablative conditioning (MAC) regimens, between 2007 and 2020, describing the survival outcome and relapse probability after achieving CR1 and CR2 and determining outcome differences in relation to indications for HSCT in patients transplanted in CR1. All patients had achieved a negative minimal residual disease prior to transplant (<0.01%).

RESULTS: Forty-six patients (68.7%) were in CR1; 25 had adverse cytogenetics, including 18 patients with Philadelphia chromosome-positive ALL (Ph-positive ALL), and 21 had poor induction response. The 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) for the whole cohort were 56.1% (95% CI, 42.8%-69.4%), 49% (95% CI, 35.7%-62.3%) and 33.5% (95% CI, 21.7%-45.8%), respectively with better EFS and CIR for CR1 transplants compared to CR2 transplants (P=0.02 and P=0.03, respectively). Patients with Ph-positive ALL had better 5-year OS, EFS and non-relapse mortality (NRM) compared with other CR1 transplants (P=0.015, P=0.009 and P=0.028, respectively).

CONCLUSION: Hematopoietic stem cell transplantation from MSD for ALL in CR1 group had superior outcomes compared to CR2 group and was apparently a curable option for Ph-positive ALL without an increased risk of non-relapse mortality. Poorer survival rates and higher relapse probabilities were associated with HSCT conducted to patients who had a poor response to induction therapy or suffered a relapse.