Iran's research prioritization: Are we meeting the goals? A study based on clinical trial registry data.

The prioritization of research topics in the health domain is a critical step toward channelling efforts and resources into areas that have received less attention. The objective of this study is to evaluate the implementation of research priorities determined at the national level within Iran for the period spanning five years between 2009 and 2013. We extracted the required data from the Iranian Registry of Clinical Trials (IRCT) website. Then we conducted a matching process between the titles of trials registered in the IRCT until December 3rd, 2013, and the list of national health research priorities in the domains of communicable and non-communicable diseases. The latter was compiled and regulated by the Research and Technology Deputy of the Ministry of Health since 2008. Out of the total 5,049 clinical trials registered in IRCT, 92.3% were carried out within the domain of non-communicable diseases, while 6.1% pertained to the field of communicable diseases and the remaining 1.3% in other fields. 56.4% of the clinical trials conducted in the field of communicable diseases and 32.8% of those conducted in the field of non-communicable diseases were consistent with the research priorities determined in these two fields. During the five-year period of the prioritization goal, there was no significant improvement in adherence to the list of priorities compared to the previous five-year period. Furthermore, certain priorities were neglected within both areas during these periods. It is possible to evaluate the effectiveness of research prioritization using the data obtained from the registration centers of clinical trials. Our study has revealed that the list of priorities has not garnered adequate attention from the research community within the country. Hence, remedial measures are imperative to ensure the priorities are given more attention after publication.

Hydroalcoholic extract of Taraxacum officinale induces apoptosis and autophagy in 4T1 breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer sub-type with limited therapeutic options. Dandelion (Taraxacum officinale) exhibiting extensive anti-cancer activity is reported to be effective against TNBC; however, its anti-tumor effect mechanisms have not been fully elucidated. The purpose of this study was to determine the anti-cancer activity of hydroalcoholic extract of dandelion (HADE) on 4T1 cells, and the mechanism of HADE-induced cell death. The effect of HADE on cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Apoptotic cell death was monitored by flow cytometry. The DNA fragmentation was evaluated by Acridine orange/Ethidium bromide (AO/EB) staining. Nitric oxide (NO) level was detected using Griess assay. The effects of HADE on Atg-7, Beclin-1, Bcl2, Bax and p53 genes were investigated by real-time reverse transcription-polymerase chain reaction. The results showed that HADE inhibited cell growth and proliferation in a dose- and time-dependent manner. The HADE induced 4T1 breast cancer cell death via apoptosis and autophagy. The DNA fragmentation was improved as the concentration of HADE increased. The NO secretion was declined with increasing concentration of HADE. Gene expression analysis confirmed HADE-induced apoptosis and autophagy in cancer cells. The Bax, Bax/Bcl-2 ratio, p53, Beclin-1 and Atg-7 over-expression as well as Bcl-2 down-regulation were also evident in treated cancer cells.

Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice.

BACKGROUND: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. OBJECTIVE: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. MATERIALS AND METHODS: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg) and Genistein plus morphine (0, 1, 2, and 3 mg/kg) were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6) and sperm parameters (sperm cells viability, count, motility and morphology), testis weight and histology, testosterone hormone (ELISA method), FSH and LH hormones (immunoradiometry) and serum nitric oxide (griess assay) were analyzed and compared. RESULTS: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg) LH and FSH level, histological parameters, count, viability (55.3%), morphology and motility of sperm cells (1%), testis weight (0.08 gr) and increase nitric oxide compared to saline group (p=0.00). However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p<0.025). CONCLUSION: It seems that Genistein administration could increase the quality of spermatozoa and prevent morphine- induced adverse effects on sperm parameters.

Diagnostic procedures for improving of the KIT (CD117) expressed allele burden for the liver metastases from uterus mast cell tumors: prognostic value of the metastatic pattern and tumor biology.

The activating KIT marker plays a central role in the pathogenesis, diagnosis, and targeted treatment of systemic mastocytosis (SM). Recent studies have identified the KIT (CD117) as a marker that distinguishes nonneoplastic from neoplastic mast cells in human systemic mastocytosis. In this study, we conclude that immunohistopathology assays for KIT staining pattern are useful complimentary tools for diagnosis and evaluation of prognosis in uterus mast cell tumor (MCT) metastasis to the liver in 10 patients. Uterine and hepatic cytology revealed mast cell neoplasia, which was confirmed as visceral mast cell tumor on postmortem examination. Histological changes of densely packed, poorly differentiated neoplastic mast cells, sheets of neoplastic round to pleomorphic cells that formed nonencapsulated nodules, high mitotic figures, necrosis, and fibrosis were found. In addition, eosinophils were scattered among the mast cells at the periphery of the nodules. These findings indicate tumors of high-grade malignancy with infiltrative cells resembling the uterus MCT in the intraparenchymal and periparenchymal areas of the liver. Immunohistochemically, tumors were positive for KIT. The histopathologic features coupled with the KIT immunoreactivity led to diagnosis of high-grade uterus MCTs. Taken together, these findings suggest that CD117 may play a critical role in early uterus MCT development and may be a stimulatory factor in grade 3 MCT. Therefore, the result has supported our hypothesis that there was an increased opportunity to observe a higher CD117 staining pattern in high-grade MCTs.

Improving the diagnosis, treatment, and biology patterns of feline mammary intraepithelial lesions: a potential model for human breast masses with evidence from epidemiologic and cytohistopathologic studies.

In this study, the frequency of different types of mammary masses and their relationship with cytohistopathologic changes was investigated and data on history, macroscopic description, clinical examination and treatment were collected. To determine the prevalence and types of cytohistopathologic changes, mammary glands from 12 female cats were evaluated. The mean age of cats at the time of diagnosis was 11.5 ± 1.9 years (range 4-14 years), the mean gross size of the masses was 3.1 ± 2.4 cm, 4/12 (33.3 %) masses were ≤3.0 cm in diameter, and the maximum diameter of the largest mass had a median of 5 cm, with a range of diameter of 6 × 5 × 4 cm. Moreover, the preferential localization of mammary masses was the abdominal lobes (%50) and thoracic lobes (%33.3), and inguinal lobes (%16.7 of cases). Furthermore, two cases of the inguinal masses affected the caudo-inguinal lobe, six cases caudo-abdominal lobe, and thoracic masses were found in four cases. Eventually, six cases (%50) of masses were found in the right mammary lobes and six cases (%50) in the left mammary lobes. The majority of the masses revealed elastic (%50 of cases), hard (%25 of cases), or soft (%25 of cases) consistency. In the present study, according to the criteria of the veterinary and the medical WHO classification system, of the 12 cats with the cytohistopathological features of six (50 %) cases qualified abscess, 3 (25 %) cases as cystic hyperplasia and 3 (25 %) cases were called situ carcinoma. Whereas, all hyperplastic lesions (case nos. 7-9 and ranging in size from, 1 to >4 cm(3)) and carcinomas in situ lesions (case nos. 10-12 and ranging in size from, 1 to >3 cm(3)) were found incidentally upon routine cytohistology. Other lesions were observed grossly and removed either at surgery (case nos. 1-6). Finally, the cats were treated with unilateral lumpectomy (3 cases) and also, nine (75 %) cases had subsequent drainage, 3 (25 %) of which showed cystic hyperplasia and 6 (50 %) showed abscess on subsequent histopathological evaluation. Therefore, a correct diagnosis must be established quickly, and treatment must be instituted rapidly when alteration is noted in the mammary glands.

Pyoderma gangrenosum: uncommon presentations.

Pyoderma gangrenosum (PG) is a rare, inflammatory, noninfective, nonneoplastic skin disorder, which is often associated with systemic diseases. These include inflammatory bowel disease, rheumatoid arthritis, paraproteinaemia, or hematologic malignancy, which can be found in up to 50% of patients with some variants of PG. Brunsting et al (Arch Dermatol 1930;22:655-80) first described PG as a disease entity in 5 patients who had painful, enlarging necrotic ulcers with bluish undermined borders surrounded by advancing zones of erythema. Four of these patients had chronic ulcerative colitis. They felt that the condition might be associated with bacterial infection (pyoderma) and considered it as linked to the underlying bowel disease. Although the cause of PG remains obscure, bacterial infection seems to be unrelated to its causation, rendering the term pyoderma redundant. In addition, the number of conditions reported in association with PG has markedly expanded in recent years, showing clearly that this is not solely a cutaneous manifestation of inflammatory bowel disease. The clinical concept of PG has also been broadened, and certain clinical variants of PG have been linked with different types of associated disease seen in these patients.

Pruritic urticarial papules and plaques of pregnancy: current status.

Pruritic urticarial papules and plaques of pregnancy is a common benign dermatosis of pregnancy that was described in 1979 as an intensely pruritic urticarial cutaneous eruption. This is a well-defined clinical entity that mainly occurs in primigravidas in the third trimester, which resolves spontaneously or with delivery and is usually responsive to topical treatments. The aetiology of PUPPP is obscure. Histology is non-specific, but consistently shows mild lymphohistiocytic perivascular inflammatory infiltrate with a variable number of eosinophils. Immunofluorescent studies are negative. The maternal and fetal prognosis are generally unaffected, and the condition is usually responsive to topical corticosteroids and oral antihistamines.

Evaluation of the penetration of 5-aminolevulinic acid through basal cell carcinoma: a pilot study.

Aminolevulinic acid (ALA) is a charged, hydrophilic molecule that penetrates poorly through cellular structures. This property has been implicated in the poor clinical response of non-superficial basal cell carcinomas (BCCs) to photodynamic therapy (PDT). Release of ALA hydrochloride from a 20% w/w formulation was found to be incomplete and that approximately 36.8% of the total dose is released during the application period of 4 h. Using scintillation spectroscopy and a precise tissue sectioning protocol, it was demonstrated that depths of penetration of at least 2 mm from the lesion surface had been reached. Using cumulative stratal ALA concentrations, it was found that 10% of the total applied dose permeated into the lesion. In spite of this, comparisons drawn with photodynamic concentrations used in tissue culture work reported elsewhere revealed that estimations of the ALA concentration at 2 mm were sufficient to elicit a possible therapeutic response. Results from this work question the reasons given for poor outcomes of PDT in nodular BCC based solely on depth as a hindering factor.