Geographic variation in urinary tract and genital cancers in Iran: a hypothesis involving exposure to solar radiation.

OBJECTIVE: Sunlight and vitamin D intake are considered as essential elements for human health. Insufficient intake of this vitamin is one of the causes of various cancers and some other diseases. The aim of this study was to investigate the relation between bladder, prostate, cervical and ovarian cancers with solar ultraviolet exposure in Iran. In this ecological study, data from 30 provinces were studied and analyzed by correlation and linear regression tests in SPSS software version 22. Physical activity, gender, human development index, lung cancer and altitude were adjusted at population level. RESULTS: The incidence of bladder cancer in both sexes was inversely related to ultraviolet radiation, but it was significant only in men. Unlike bladder cancer, the incidence of cervical cancer showed a positive relation with ultraviolet radiation. No relation was found between the incidence of prostate and ovarian cancers with ultraviolet radiation. Among the adjusting variables, the incidence of lung cancer (surrogate for smoking) in women had the highest coefficient in the linear regression model.

Clinical presentations, diagnosis, management, and outcomes of renal mucormycosis: An overview of case reports.

Background: Renal mucormycosis (RM) is a rare presentation of invasive mucormycosis with a high mortality rate. There is no single systematic review of the literature that indicates the different clinical aspects of RM. Methods: A systematic search of PubMed/Medline was performed to collect individual case reports of RM in patients of all ages published between 2010 and April 2022. Results: Seventy-one individual cases were detected through PubMed bibliographic database searches, with a final assessment performed on 60 patients with RM. India and Asia had the largest number of reported cases, with 30 (50%) and 42 (70%) reports, respectively. Also, 74 and 26% of the patients with a mean age of 33 years were male and female, respectively. RM showed 44% mortality rate in the analyzed cases. Immunosuppressive agent therapy followed by tissue transplantation (kidney and liver) and diabetes were the most remarkable risk factors in patients. Nevertheless, 22% of the patients were immunocompetent with no apparent underlying condition. COVID-19 positivity was detected in eight adult patients with an 87% mortality rate. The most common signs of infection were fever, flank pain, and oliguria; additionally, isolated RM was reported in 57% of the cases. In 55% of the patients, histopathologic examination alone was sufficient to diagnose RM, whereas molecular methods and culture were used in only 18 and 35% of patients, respectively. Surgery alone, surgery plus anti-infection therapy, and anti-infection therapy alone were used in 12, 60, and 13% of patients, respectively. Furthermore, 15% of the patients died before any treatment. Conclusion: The early diagnosis of RM is necessary. In this regard, the use of molecular-based diagnostic assays can help identify the fungus at the genus and species levels and use an appropriate treatment in the shortest possible amount of time. Because of the increase in antibiotic resistance in recent years, determining microbial susceptibility tests can lead to the better infection management. Additionally, withdrawal of immunosuppressant, appropriate surgical intervention, and antifungal therapy are the main factors associated with a successful outcome in RM.

Comparison of High-Resolution Melting (HRM) Analysis with Direct Sequencing for the Detection of DNMT3A Mutations in AML Patients.

OBJECTIVE: Acute myeloid leukemia (AML) is caused by abnormal gene expression following mutations. Many of the mutations in AML lead to gene instability and poor response to treatment. Among these mutations, DNMT3A mutation is exceedingly important due to its major role in methylation and its effect on the expression of other genes. Aberrant methylation due to DNMT3A mutations that mostly occur in exon 23, affects the overall survival (OS) of patients with AML and myelodysplastic syndromes (MDS) showing the importance of identification of these mutations. According to the association of these mutations with short overall survival and disease progression in AML patients, we aimed to investigate DNMT3A gene exon 23 mutations using HRM. METHODS: Fifty peripheral blood samples were taken from patients with AML. Mononuclear cells were isolated by ficoll method, and DNA was extracted. Then, mutation detection was detected using the HRM method. Efficacy of the HRM method in mutation detection was compared with direct sequencing method as gold standard. RESULTS: Mutations in codon 23 of the DNMT3A gene were detected in 5 patients (10%). All of the detected mutations were missense type. A comparison between direct sequencing and HRM analysis demonstrated full concordance of mutation detection. CONCLUSION: According to the full consistency between the HRM and direct sequencing methods, HRM is suggested to be adopted as an alternative for the common time-consuming methods in detecting the gene mutations.

Isolation of a lytic bacteriophage against extensively drug-resistant Acinetobacter baumannii infections and its dramatic effect in rat model of burn infection.

OBJECTIVES: Acinetobacter Baumannii is an opportunistic nosocomial pathogen belonging to the Moraxellaceae family. The emergence of multidrug resistant strains of this pathogen caused many problems for hospitals and patients. The aim of the current study was to isolate, identify, and morphologically, physiologically, and in vivo analyze a new lytic bacteriophage targeting extensively drug-resistant (XDR) A. baumannii. MATERIALS AND METHODS: Different wastewater samples were tested for isolation of lytic bacteriophage against 19 A. baumannii isolates obtained from patients hospitalized in a hospital in Arak, Iran, from January 2019 to March 2019. The phenotypic and genotypic characteristics of A. baumannii strains (resistance genes including: adeA, adeB, adeC, adeR, adeS, ISAba1, blaOXA-23, blaOXA-24) were analyzed. The isolated phage characteristics including adsorption time, pH and thermal stability, host range, one-step growth rate, electron microscopy examination, and therapeutic efficacy of the phage were also investigated. Therapeutic efficacy of the phage was evaluated in a rat model with burn infection of XDR A. baumannii. The lesion image was taken on different days after burning and infection induction and was compared with phage untreated lesions. RESULTS: The results showed unique characteristics of the isolated phage (vB-AbauM-Arak1) including high specificity for Acinetobacter baumannii, stability at a relatively wide range of temperatures and pH values, short adsorption time, short latent period, and large burst size. In relation to the therapeutic efficacy of the phage, the lesion area decreased in phage-treated groups over 14 days than in those untreated, significantly (p < 0.05). CONCLUSION: Our findings demonstrated that isolated lytic phage was able to eliminate burn infections caused by XDR A. baumannii in a rat model. So, it may be recommended as alternative options toward to developing a treatment for extensively drug resistant Acinetobacter infections.

Rapid Detection of N-RAS Gene Common Mutations in Acute Myeloid Leukemia (AML) Using High Resolution Melting (HRM) Method.

OBJECTIVE: Acute myeloid leukemia is caused by the clonal proliferation of undifferentiated myeloid hematopoietic precursors. AML prognosis is highly involved in the treatment response and is determined by mutations in several genes such as N-RAS. This study aims to identify the distribution of common N-RAS mutations (codons 12, 13, and 61) in AML patients using the HRM method and confirm this method's efficiency for mutation detection by comparing its results with the sequencing data as the Gold standard method. METHODS: Peripheral blood samples were taken from 50 newly diagnosed AML patients. Mononuclear cells were isolated from samples, and DNA was extracted. Then, mutation detection was investigated using the HRM method. Efficacy of the HRM method in mutation detection was determined in comparison with direct sequencing. RESULTS: N-RAS mutations were detected in 7 of the 50 samples (14%). Most of the mutations were found in codon 12 (57.14%), and 28.57% and 14.28% of mutations were in codons 61 and 13, respectively. There was no statistically significant association between patients' demographic data and HRM results. CONCLUSION: According to mutation detection results and the HRM results confirmation with the sequencing method, this method can be introduced as an efficient, low-cost, and fast method for detecting common mutations.

Gastrointestinal mucormycosis: A periodic systematic review of case reports from 2015 to 2021.

BACKGROUND: GI mucormycosis (GI) is a rare but highly lethal infection in patients. There is no single comprehensive review of the literature that demonstrates the various clinical aspects of this infection. METHODS: A structured search of PubMed/Medline was used to collect case reports of GI mucormycosis in patients of all ages published between 2015 and November 2021. RESULTS: Eighty-seven cases were identified through PubMed bibliographic database searches, and final analyses were conducted on 70 adults and ten neonatal patients with GI mucormycosis. Asia had the highest number of reported cases, with 46 (57.5%). Neonatal cases had a mortality rate of 70%, while other cases had a mortality rate of 44%. Corticosteroid therapy and diabetes were the most significant risk factors in patients, while 11% were immunocompetent with no apparent underlying condition. COVID-19 positivity was detected in four adult patients. Moreover, neonatal cases included premature and low-weight infants, metabolic acidosis, and malnutrition. Abdominal pain, fever, and GI perforation were the most common signs of infection, while vomiting occurred in 40% of neonatal cases. In 97% of patients, a histopathologic examination was used to detect infection, whereas culture and molecular methods were used in only 28% and 17% of patients, respectively. Surgery plus anti-infection therapy, anti-infection therapy alone, and surgery alone were used in 61%, 28%, and 11% of patients, respectively. Nonetheless, all neonatal patients underwent surgery. Although used in a small number of patients, posaconazole (30%) and isavuconazole (11%) demonstrated high efficacy in treating patients. CONCLUSION: GI mucormycosis is a rare but highly lethal disease. Treatment of underlying conditions, the use of multiple diagnostic techniques, and appropriate antifungals in conjunction with surgery can all contribute to infection control.

CXCL1, CXCL10 and CXCL12 Chemokines are Variously Expressed in Acute Myeloid Leukemia Patients Prior and Post Bone Marrow Transplantation.

AIM: The chemokine-receptor axes play parts in development of leukemia, CXCL1, CXCL10 and CXCL12 are involved in immune responses. Thus, we have examined the serum levels of these chemokines in parallel with their related cognate receptors (CXCR1, CXCR3 and CXCR4) in AML (acute myeloid leukemia) patients prior and post BMT (bone marrow transplantation) therapy. MAIN METHODS: Clinical specimens were collected from 46 AML patients (23 M1 and 23 M3 subtypes) before/after BMT. CXCL1, CXCL10 and CXCL12 concentrations were determined by ELISA. The mRNA levels of the related receptors were detected by QRT_PCR. Data were analyzed by T-test, χ2 and ANOVA statistical methods in SPSS software version 18. A difference was regarded significant if P value < 0.05. KEY FINDINGS: Our results indicated that the elevated levels of CXCL12 in AML patients were remained unchanged after transplantation.  The CXCL10 concentration was decreased in patients. All studied chemokines were elevated in BMT patients with history of 9 times PLT transfusion. In patients who received BMT from siblings CXCL1 and CXCL10 have been elevated, whereby they were compared to patients who received BMT from parents while CXCL12 sustained unchanged in groups. Serum measures of CXCL1 and CXCL10 were induced in acute and chronic GVHD patients in compare to these without GVHD. SIGNIFICANCE: According to the results, it can be concluded that these chemokines play fundamental parts in pathogenesis of both AML and BMT. It is worthy to note that chemokines could be used as diagnostic markers alongside with possible promising therapeutic targets.

High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene.

BACKGROUND: Pentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm). RESULT: The nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment. CONCLUSION: According to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.

Comparison of high-resolution melting analysis with direct sequencing for detection of FLT3-TKD, FLT3-ITD and WT1 mutations in acute myeloid leukemia.

BACKGROUND: Acute Myeloid Leukemia (AML) is a group of hematologic diseases characterized by a variety of clinically important genetic alterations. Genetic mutations affecting the FMS-like receptor tyrosine kinase-3 (FLT3) and Wilm's tumor (WT-1) genes are associated with poor prognosis in AML. In this work, efficiency of HRM method for detection of FLT3-ITD, FLT3-TKD, and WT-1 mutations was assessed in comparison with direct sequencing. METHOD: A total of 58 formalin-fixed, paraffin-embedded BM biopsy specimens of AML patients were analyzed. Mutation detection was performed by HRM method and the results were consequently compared with direct sequencing RESULTS: FLT3 and WT-1 mutations were detected in 21 (36.2%) and 3 (5.17%) samples, respectively. Among all FLT3 mutations, 10 (17.2%) and 11 (18.2%) samples were harboring the FLT3-ITD and-TKD gene mutations, respectively. Frequency of the FLT3-ITD was not statistically different in females (51%) and males (49%). Also, FLT3-TKD was more common in males although the differences in gender distribution were not statistically significant (P = 0.721 and P = 0.626, respectively). CONCLUSIONS: Regarded as the desirable characteristic, the present study is generally distinguished by the similar previous ones due to assessing the FFPE BM tissue from the perspective of the type of assessed sample. This discrepancy between our results and those in prior studies may be due to the disparity of the studied population size, adopted methods as well as the sample type. In this survey, regarding to low amount of extracted DNA from the paraffinized samples, the HRM method was efficient in determining the mentioned mutations.

Alterations in The Plasma Expression of mir-15b, mir-195 and the Tumor-Suppressor Gene DLEU7 in Patients with B-Cell Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is one of the most prevalent forms of leukemia in adults. Inactivation of the DLEU7 gene is frequently observed in patients with CLL. Furthermore, microRNAs (miRNAs) have been observed to have a critical role in the pathogenesis of several cancers, including leukemia. Considering the tumor-suppressive role of DLEU7, as well as the tumor suppressor or oncogenic role of microRNAs (miRNAs), the aim of the present study was to evaluate the potential miRNAs targeting the DLEU7 gene in B-cells and explore expression changes these genes in the plasma of B-CLL patients. METHODS: The miRNAs interacting with the DLEU7 gene were predicted and selected using bioinformatics tools. A total of 80 plasma samples were collected from 40 patients with B-cells and 40 healthy individuals, then subjected to RNA extraction and cDNA synthesis. The expression profiles of the predicted miRNAs and the DLEU7 gene in the plasma of B-CLL patients and healthy individuals were determined by RT-qPCR analysis. RESULTS: The bioinformatics prediction indicated that miR-15b and miR-195 target the DLEU7 gene. The expression levels of miR-15b and miR-195 were significantly higher in the plasma of patients with B-CLL compared to the healthy individuals (91.6, p= 0.001) (169, p= 0.001). However, the expression level of the DLEU7 gene was found to be significantly lower in the patient group compared to healthy controls (0.304, p= 0.001). CONCLUSION: Both miR-15b and miR-195, have the potential to function as novel and non-invasive biomarkers in the diagnosis and prognosis of patients with B-CLL.

Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: a systematic review of case reports.

BACKGROUND: Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). METHODS: Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline. RESULTS: Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%). CONCLUSION: CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.

Investigation into antibacterial and wound healing properties of platelets lysate against Acinetobacter baumannii and Klebsiella pneumoniae burn wound infections.

BACKGROUND AND AIM: Treatment of burn wound infections has become a global challenge due to the spread of multidrug-resistant bacteria; therefore, the development of new treatment options for the mentioned infections is essential. Platelets have drawn much attention for this purpose because they are a safe and cost-effective source of different antimicrobial peptides and growth factors. The present study evaluated antibacterial effects and wound healing properties of Platelet-derived Biomaterial (PdB) against Acinetobacter baumannii and Klebsiella pneumoniae burn wound infections. METHODS: PdB was prepared through the freezing and thawing process and then, in vitro antibacterial effect was determined by disk diffusion and broth microdilution methods. Afterward, burn wound was inflicted on 56 rats, infected with both bacteria, and topical administration was performed to evaluate antibacterial effects and wound healing properties of PdB. RESULTS: In vitro results showed that PdB inhibited the growth of A. baumannii in the highest dose (0.5), while we did not detect any inhibitory effects against K. pneumoniae. By contrast, PdB significantly inhibited the growth of bacteria in treated animal wounds compared to the control groups (P value < 0.05). Macroscopic assessments pointed to the significant enhancement of wound closure in the treated animals. In addition, histopathological examination demonstrated that treatment of rats with PdB led to a considerable increase in re-epithelialization and attenuated the formation of granulation tissue (P value < 0.05). CONCLUSION: The use of topical PdB is an attractive strategy for treating A. baumannii and K. pneumoniae burn wound infections because it inhibits bacterial growth and promotes wound healing properties.

Bacteriophage therapy for inhibition of multi drug-resistant uropathogenic bacteria: a narrative review.

Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage-host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.

Diagnostic Value of Plasma miR-145 and miR-185 as Targeting of the APRIL Oncogene in the B-cell Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide. This cancer has a poor prognosis at different stages. So, the identification of new biomarkers is important for diagnosis of B-CLL. Considering the oncogenic role of APRIL molecule in this leukemia as well as the regulatory role of miRNAs in different signaling pathways, the present study evaluated the miRNAs targeting APRIL gene in B-CLL. METHODS: The miRNAs were predicted and selected using bioinformatics algorithms. A total of 80 plasma samples were subjected to RNA extraction and synthesis of cDNA. The expressions levels of predicted miRNAs and APRIL gene in plasma of B-CLL patients and healthy individuals were assessed by Real time PCR analysis. ROC analysis was performed to investigate the role predicted miRNAs as novel biomarkers in diagnosis of B-CLL. RESULTS: The results of the prediction showed that miR-145-5p and miR-185-5p target the APRIL gene. The expression level of APRIL gene was strikingly higher in plasma of B-CLL patients than in the healthy individuals (102, P= 0.001). On the other hand, expression levels of miR-145-5p and miR-185-5p were strikingly lower in B-CLL patients than in the healthy individuals (0.07, P= 0.001) (0.29, P= 0.001). Also, ROC curve analyses demonstrated that miR-145-5p and miR-185-5p are specific and sensitive and may serve as new biomarkers for the detection of B-CLL. (AUC; 0.95, sensitivity; %90) (AUC; 0.87, sensitivity; %63). CONCLUSION: These data suggest that miR-145-5p and miR-185-5p target the APRIL gene and might have a role in diagnosis of B-CLL. Therefore, these two miRNAs can be served as a novel and potential biomarker for detection of B-CLL.

An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies.

In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes.

Significance of CXCL12/CXCR4 Ligand/Receptor Axis in Various Aspects of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is defined as an aggressive disorder which is described by accumulation of immature malignant cells into the bone marrow. Chemokine-receptor axes are defined as factors involved in AML pathogenesis and prognosis. The chemokine receptor CXCR4 along with its ligand, CXCL12 fit in important players that are actively involved in the cross-talk between leukemia cells and bone marrow microenvironment. Therefore, according to the above introductory comments, in this review article, we have focused on delineating some parts played by CXCL12/CXCR4 axis in various aspects of AML malignancy. Targeting both leukemic and stromal cell interaction is nowadays accepted as a wide and attractive strategy for improving the outcome of treatment in AML in a non-cell autonomous manner. This strategy might be employed in a wide variety of AML patients regardless of their causative mutations. In addition to several potential targets involved in the disruption of malignant leukemic cells from their specific protective niches, compounds which interfere with CXCL12/CXCR4 axis have also been explored in multiple early-phase established clinical trials. Moreover, extensive research programs are exploring novel leading mechanisms for leukemia-stromal interactions that appear to find out novel therapeutic targets within the near future.

Correlation of Cardiac and Liver Iron Level with T2*MRI and Vitamin D3 Serum Level in Patients with Thalassemia Major.

INTRODUCTION: Thalassemia is a hypochromic microcytic anemia, which is characterized by congenital disorders. In thalassemia patients, bone diseases are one of the causes of mortality. Our goal was to investigate the association between vitamin D deficiency and increased iron uptake by cardiac myocytes and hepatocytes. MATERIALS AND METHODS: Forty patients with thalassemia major were studied in Amir Kabir Hospital, Arak, Iran. The information obtained through clinical examination. Serum ferritin level was determined by ELISA and T2*MRI performed for measuring iron content in the heart and the liver. RESULTS: The average age of the patients was 23.8 ± 10.7 years. The mean T2*MRI values were 23.7 ± 7. The vitamin D3 level in 33 patients (82.5% cases) was less than 20 ng/dl, 2 patients (5%) in the range of 20-30 ng/dl, and the others had above 30 ng/dl. Correlation between vitamin D and age was 0.611. Correlation coefficient between heart and liver T2*MRI with ferritin level in patients was 0.437 and 0.335, respectively. CONCLUSION: Due to significant associations, the periodic measurement of vitamin D, as well as PTH, is recommended for patients with thalassemia major.

Wound healing properties and antimicrobial activity of platelet-derived biomaterials.

We analyzed the potential antibacterial effects of two different PdB against methicillin-resistant S. aureus and P. aeruginosa. The third-degree burn wound healing effects of PdB was also studied. Blood samples were obtained from 10 healthy volunteers and biological assays of the PdB were performed and the antimicrobial activity against MRSA and P. aeruginosa was determined using disk diffusion (DD), broth microdilution (BMD), and time-kill assay methods. 48 Wistar albino rats were burned and infected with MRSA. Two groups were injected PdB, the control groups were treated with plasma and received no treatment respectively. In the next step, the rats were euthanized and skin biopsies were collected and histopathologic changes were examined. The results of DD and BMD showed that both PdB performed very well on MRSA, whereas P. aeruginosa was only inhibited by F-PdB and was less susceptible than MRSA to PdBs. The time-kill assay also showed that F-PdB has an antibacterial effect at 4 hours for two strains. Histopathological studies showed that the treated groups had less inflammatory cells and necrotic tissues. Our data suggest that PdB may possess a clinical utility as a novel topical antimicrobial and wound healing agent for infected burn wounds.

Evaluation of MDR1 and MRPA genes expression in different types of dry cutaneous leishmaniasis.

OBJECTIVE: The resistance to antimony-containing glucantime is a major obstacle to successful treatment, especially in endemic areas. Looking the molecular mechanisms involved in this drug resistance will help in choosing the best treatment. The aim of this study was to evaluate the expression of multidrug-resistance 1 (MDR1) and multidrug-resistance protein A (MRPA) genes in acute, chronic non-lupoid, and chronic lupoid forms of dry type cutaneous leishmaniasis (DTCL). RESULTS: MDR1 gene was over-expressed as 14.4- and 1.56-folds in the chronic lupoid and acute forms compared with the chronic non-lupoid form, respectively. Results comparison showed P < 0.05 between the chronic non-lupoid and acute groups, P < 0.01 between acute and chronic lupoid groups, and P < 0.001 between the chronic non-lupoid and chronic lupoid groups. MRPA gene was over-expressed as 266 and 17.7-fold in the chronic lupoid and chronic non-lupoid forms compared with the acute form, respectively. Statistical analysis showed P < 0.01 between the chronic non-lupoid and chronic lupoid groups, P < 0.05 between acute and chronic non-lupoid groups, and P < 0.001 between the acute and chronic lupoid groups.

Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review.

The word of hemoglobinopathy is described for an array of disorders that affecting hemoglobin (Hb) functions. Hb is a molecule with 68 kDa molecular weight, serving as oxygen carrying metalloprotein. Hemoglobinopathy includes a wide range of Hb structural deficits varying from thalassemia to sickle cell disease. Cyto-chemokine network members are pivotally involved in the pathogenesis of hemoglobinopathies, however, the exact role of these mediators in the development of these disorders yet to be well addressed. Cytokines and chemokines are generated by inflamed endothelial cells that promote the expression of their respected receptors and further activate NF-κß, recruit red blood cells (RBCs) and white blood cells (WBCs) toward the inflamed endothelium. Therefore, due to critical roles played by the cyto-chemokine network in several aspects of hemoglobinopathies pathophysiology including apoptosis of endothelial cells, RBC, WBC and etc.…, in the present review, we focused on the critical parts played by this network in the pathogenesis of hemoglobinopathies.