Development of Low-Serum Culture Media for the in Vitro Cultivation of Theileria annulata S15 Cell Line.

Background: The production of bovine theileriosis vaccine involves in vitro cultivation of Theileria annulata schizont-infected cell lines. Fetal bovine serum (FBS) is commonly used in animal cell culture, including the Theileria cell line. However, we aimed to reduce the amount of serum needed for cell culture by modifying the Stoker culture medium with supplements such as excretion factor and serum substitutes. Methods: To evaluate the effectiveness of these modifications, techniques such as cell counting, cell viability assays, and genomic analysis were employed in the Parasitic Vaccines Production Department of Razi institute of Iran, from 2020 to 2022. Statistical analysis was used to compare the results of different experimental conditions. Results: The three experimental media were as effective as the commonly used 10% Stoker medium in supporting the growth and viability of cells. Conclusion: The significant reduction in the required amount of serum and the remarkable cell growth achieved by using defined serum replacements for the production of cell culture media is a significant step towards the preparation of a proper cell culture medium for the production of bovine Theileriosis vaccine.

Molecular identification of Theileria spp. in ruminants and ticks from southern littoral of Caspian Sea, Iran.

The present study aimed at evaluating the presence of tick-borne apicomplexan parasites including Theileria ovis, Theileria lestoquardi, Theileria annulata, and Theileria orientalis in 92 cattle and 105 sheep from 6 different districts of Guilan and Mazandaran Provinces, in the southern littoral of Caspian Sea. Furthermore, ixodid ticks were collected from the same animals. Stained blood smears were microscopically evaluated for the presence of blood parasites, and a specific PCR was applied for the detection of Theileria species. Besides, ticks were subsequently examined by species-specific PCR. Microscopic examination of blood smears demonstrated no evidence of intraerythrocytic piroplasms. Species-specific diagnostic PCRs demonstrated that 52.17% of sheep blood samples were positive for T. ovis. In addition, 31.03% and 24.13% of cattle blood samples were positive for T. annulata and T. orientalis, respectively. Moreover, 3 species of the ixodid ticks, namely, Rhipicephalus annulatus (58.47%), Ixodes ricinus (29.82%), and Haemaphysalis inermis (11.69%), were identified in Guilan Province, while Hyalomma detritum (73.03%) and Rhipicephalus sanguineus (26.92%) were found in Mazandaran Province. Additionally, by obtaining the data with respect to tick-borne apicomplexan parasites in 122 infected ticks, 35.24%, 22.95%, and 2.45% of tick samples were positive for T. annulata, T. orientalis, and T. ovis, respectively. Species-specific PCR revealed that H. inermis and R. annulatus were positive for T. orientalis. In addition, T. annulata was found in R. annulatus, H. inermis, and H. detritum. Besides, T. ovis was the only species of Theileria found in R. sanguineus. In conclusion, the results revealed that T. annulata infection was prevalent among cattle and ovine theileriosis caused by T. ovis was the only Theileria species found in sheep in the studied areas of the southern littoral of Caspian Sea. R. annulatus, H. inermis, and H. detritum were the main vectors for T. annulata, followed by H. inermis and R. annulatus for T. orientalis, and R. sanguineus for T. ovis.

Evaluation of Cellular Immune Responses in Dogs Immunized with Alum-Precipitated Autoclaved Leishmania major along with BCG and Imiquimod.

BACKGROUND: We aimed to investigate the potential effects of BCG and imiquimod on improvement of current experimental L. major vaccine against dogs in an endemic area of Zoonotic visceral leishmaniasis (ZVL) in Iran. METHODS: During 2012 till 2014, seven mixed-breed shepherd dogs with no anti-Leishmania antibodies and no response to Leishmanin reagent were immunized with 2 doses of alum-precipitated autoclaved L. major (Alum-AML) while BCG and imiquimod (for skin pre-treatment) were used as adjuvants. The productions of a few characteristic cytokines of T-helper immune responses and the development of delayed-type hypersensitivity (DTH) of the immunized animals were then evaluated, up to 300 days. Blood samples were collected at 0, 30, 80 and 300 d post-vaccination and the concentrations of IFN-γ, IL10, IL-12 and TGF-ß cytokines secreted from PBMCs at these time-points were quantified by ELISA. DTH was evaluated by Leishmanin skin test (LST). RESULTS: Although a similar LST conversion was observed at all time-points, the cytokine measurement results indicated significantly higher levels of IFN-γ at day 80 and elevated levels of IL-10 at days 80 and 300, post-vaccination. Moreover, a significantly higher IFN-γ/IL-10 ratio was observed at day 30 post-vaccination compared to the other time-points. CONCLUSION: Although a Th1-like response could be observed at day 30 post-vaccination, the development of cytokine profiles was inclined toward mixed Th1 and Th2 responses at days 80 and 300 post-vaccination. This situation may indicate the requirement of an additional boosting by this Alum-AML formula, in order to induce long-lasting protection against ZVL.

Babesia canis caused clinical babesiosis in a female Shih Tzu dog.

A 2-year-old female Shih Tzu dog was submitted with the history of anorexia and depression for one week and no prior surgery. Fever and pale mucosa were noticed in physical examination. Microscopic examination of the Giemsa-stained blood smear disclosed large form of Babesia and single to four pear-shaped merozoites within erythrocytes (RBCs). Regenerative anemia characterized by a marked reticulocytosis, significant intra-vascular hemolysis, nucleated RBCs, left-shifted neutrophils, thrombocytopenia, azotemia, high serum creatinine and urea concentrations were recorded following hemato-biochemical analysis. Abundant bilirubin crystals and abnormal reddish color after centrifugation were observed in urinalysis. Molecular analysis was performed using specific primers for detection of Babesia canis. Diminazene aceturate, ciprofloxacin, ivermectin and phosphorus-vitamin B12 were prescribed and the clinical signs improved after four days. Two months follow-up showed no recurrence. Such studies would significantly contribute to the development of appropriate preventive strategies and successful treatment. This communication reports a clinical case of canine babesiosis caused by B. canis in a female Shih Tzu dog.

Detection and Molecular Characterization of Babesia canis vogeli and Theileria annulata in Free-Ranging Dogs and Ticks from Shahriar County, Tehran Province, Iran.

BACKGROUND: We aimed to detect and characterize vector-borne parasites of Babesia and Theileria in dog and ticks by PCR assay. Canine babesiosis is a significant tick-borne disease caused by different Babesia species. As the infection has not been reported in Shahriar region Tehran, Iran, molecular techniques allowed us to identify tick-borne parasites in asymptomatic dogs. METHODS: The number of 40 dog peripheral blood samples and 27 skin attached ticks were analyzed by molecular PCR assay. The specific primers were used for detecting Babesia canis, B. gibsoni and T. annulata. RESULTS: B. c. vogeli was detected in 10 dog blood samples (25%). Additionally, T. annulata infection was identified in 13 dog blood samples (32.5%) and 18 isolated tick DNAs (66.7%). The results of PCR were confirmed by 18S rRNA and Tams1 gene sequence analyzing and have been registered in GenBank under following accession numbers for B. c. vogeli (MH793502) and T. annulata (MK105284). Conclusion: The verification of T. annulata infection in free-ranging dogs and ticks shows dogs might be considered as important natural carriers/reservoirs for T. annulata in enzootic region for bovine theileriosis. The obtained data may be useful for veterinary practitioners and dog owners to aware of Babesia and Theileria infection in dog and tick to establish the effective preventive measures.

Establishment and Validation of Theileria annulata Sporozoite Ak-93 Infection in Laboratory-Reared Hyalomma anatolicum Tick Using In Vivo and In Vitro Assays.

BACKGROUND: Tropical Theileriosis caused by Theileria annulata is a tick-borne disease which transmitted by the ixodid tick members of the genus Hyalomma. Studies on different aspects of disease require to access infective sporozoite of parasite which produced by tick vector. This study was carried out to establish of T. annulata life cycle to achieve T. annulata infected ticks. METHODS: Laboratory rabbit and calf were used for rearing of Hyalomma anatolicum different instars. Unfed nymphs were fed on T. annulata infected calf. Clinical signs, Giemsa stained smears and Polymerase Chain Reaction (PCR) methods were used for detection of infection in blood and tick specimens. Susceptible calf was used for confirmation of sporozoites maturation and infectivity in bioassay test. RESULTS: Hyalomma anatolicum two and three-host strategies of life cycle was lasted 90 and 116 days respectively. The PCR confirmed T. annulata infection in blood and tick samples. Maturation of T. annulata sporozoites was confirmed in bioassy test. First clinical symptom of disease was seen earlier in the case of transmission of disease through feeding of live ticks in comparison with blood injection method. CONCLUSION: Complete life cycle of T. annulata was done and confirmed by clinical signs, microscopic examination, molecular methods and bioassay test. According to published reports to date, this is the first report of establishment of H. anatolicum tick infection with T. annulata using susceptible calf under controlled conditions in Iran.

Determination of the Infectivity of Cryopreserved Theileria annulata Sporozoites in Tick Derived Stabilates Iran Ak-93 Strain, by In Vivo and In Vitro Methods.

BACKGROUND: The protozoan parasite Theileria annulata is the causative agent of tropical theileriosis in cattle. Vaccination is recommended by administration of attenuated schizont-infected cell lines. The expected protective immunity post-vaccination can be demonstrated by challenge test through inoculation of highly virulent infective sporozoites. The aim of this study was to produce Hyalomma anatolicum anatolicum tick infected with T. annulata (local strain) for preparation of tick-derived sporozoite stabilates for molecular characterization and infectivity test assay. METHODS: A local T. annulata strain was used for experimental infection of calves. A field isolate of H. a. anatolicum was isolated, laboratory-reared and infected by blood-feeding on Theileria infected above-mentioned calves. The infectivity of calf, tick and prepared stabilate were confirmed by clinical signs of theileriosis, microscopic inspection, RT-PCR and in vitro cell culture. RESULTS: The tick stabilate was prepared and cryopreserved in liquid nitrogen. The infectivity of the tick stabilate was verified by in vivo bioassay, in vitro cell culture infection, microscopic inspection in salivary glands and RT-PCR assay. The in vitro produced cell line in this study was characterized by T. annulata Cytochrome b gene analyzing. CONCLUSION: The infectivity of a new prepared tick-derived sporozoite stabilate was confirmed in susceptible calves; by microscopically, post mortem, tick microscopic and molecular assays. Moreover, naïve PBMCs were transformed and proliferated by T. annulata infected tick stabilate to immortal T. annulata schizont infected cell line. The potent infective sporozoite tick derived stabilate could be used for vaccine efficacy and challenge test as well as in vaccine development.

The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome.

Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative. BALB/c mice were immunized by liposomal formulations of lip/SLA, lip/MPL/SLA, lip/IMQ/SLA, lip/MPL/IMQ/SLA, lip/SLA + lip/IMQ, lip/SLA + lip/MPL, lip/SLA + lip/MPL/IMQ and five controls of SLA, lip/MPL, lip/IMQ, lip/MPL/IMQ and buffer by subcutaneously (SC) injections, three times in 2 weeks intervals. The synergic effect of two adjuvants when they are used in one formulation showed significantly (p < .001) smaller footpad swelling and the lowest parasite burden in lymph node and foot after the challenge. IgG2a in these groups showed the higher titre compared to control groups, which is compatible with the high IFN-γ production and lowest IL-4. Taken together the results indicated that co-delivery of MPL and IMQ adjuvants and antigen in nanoliposome carrier could be an appropriate delivery system to induce cellular immunity pathway against leishmaniasis.

Isolation and purification of glycosylphosphatidylinositols (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals.

BACKGROUND: Tropical theileriosis is widely distributed from North Africa to East Asia. It is a tick-borne disease caused by Theileria annulata, an obligate two-host intracellular protozoan parasite of cattle. Theileria annulata use leukocytes and red blood cells for completion of the life-cycle in mammalian hosts. The stage of Theileria annulata in monocytes and B lymphocytes of cattle is an important step in pathogenicity and diagnosis of the disease. Glycosylphosphatidylinositols (GPIs) are a distinct class of glycolipid structures found in eukaryotic cells and are implicated in several biological functions. GPIs are particularly abundant in protozoan parasites, where they are found as free glycolipids or attached to proteins in the plasma membrane. RESULTS: In this study we first isolated and purified schizonts of Theileria annulata from infected leukocytes in Theileria annulata vaccine cell line (S15) by aerolysin-percoll technique. Then, the free GPIs of schizont stage and isolated GPI from cell membrane glycoproteins were purified by high performance liquid chromatography (HPLC) and confirmed by gas chromatography-mass spectrometry (GC-MS). Furthermore, enzyme linked immunosorbent assay (ELISA) on the serum samples obtained from naturally infected, as well as Theileria annulata-vaccinated animals, confirmed a significant (P < 0.01) high level of anti-GPI antibody in their serum. CONCLUSIONS: The results presented in this study show, to our knowledge for the first time, the isolation of GPI from the schizont stage of Theileria annulata and demonstrate the presence of anti-GPI antibody in the serum of naturally infected as well as vaccinated animals. This finding is likely to be valuable in studies aimed at the evaluation of chemically structures of GPIs in the schizont stage of Theileria annulata and also for pathogenicity and immunogenicity studies with the aim to develop GPI-based therapies or vaccines.

Scientometric analysis and mapping of 20 years of glaucoma research.

AIM: To provide a scientometric analysis in the field of glaucoma. METHODS: A bibliometric method was used to obtain a view of the scientific production in field of glaucoma by data extracted from the Institute for Scientific Information (ISI) from 1993 to 2013. Specific parameters were retrieved from the ISI. Articles about glaucoma were analyzed regarding the topics' structure, history, and document relationships using HistCite software. Also, the trends in the most influential publications and authors were analyzed. RESULTS: The number of articles was constantly increasing, and most highly cited articles addressed clinical and epidemiologic topics in this field. During the past three years, there has been a trend towards genomic research studies and also more molecular translational research. CONCLUSION: This was the first scientometric report on glaucoma, analyzing the characteristics of papers and the trends in scientific production. A constant increase was observed in the number of papers, while the subject of papers had a shift in the past three years towards genomic research studies.

Microscopic and Molecular Detection of Theileria (Babesia) Equi Infection in Equids of Kurdistan Province, Iran.

BACKGROUND: Equine piroplasmosis (EP) is the cause of persistent tick-borne infection with no symptoms, but the most important problem of EP is due to the persistent carrier state. Carrier animals to Babesia (Theileria) equi (Laveran 1901) and B. caballi (Nuttall, 1910) infestation could be identified by extremely sensitive PCR-based method. The purpose of this study was to identify the causative agents of equine piroplasmosis based on molecular and microscopic assays in equids from Kurdistan Province, Iran. METHODS: Thirty one horse and mule blood samples were used with history of living in Kurdistan Province of Iran. The blood specimens were utilized for T. equi and B. caballi DNA identification by PCR and Giemsa stained smears for microscopic observation. RESULTS: The results clearly showed the presence of B. (Theileria) equi DNA in 30 of 31 blood samples (96.77%), but the microscopic examination revealed the 3 of 31 positive Babesia like organisms in the red blood cells (9.67%). CONCLUSION: The obtained results demonstrated the presence of hidden B. (Theileria) equi infection in horses with previous habitance in Kurdistan Province of Iran. The carrier animals became a main source of infection and can transmit the disease. Therefore, hidden infection might be considered as a health threatening and limiting factor in animals used in therapeutic antisera research and production centers.

Age-Related Macular Degeneration: A Scientometric Analysis.

Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning.

Immunological analysis of aerobic bioreactor bovine theileriosis vaccine.

BACKGROUND: In this study, the pilot production of aerobic bioreactor tropical theileriosis vaccine was optimized with the aim of immunological assays for further mass production. METHODS: We have shown earlier the delayed type hypersensitivity (DTH) assay could be used for evaluating the immunity and memory cells against specific Theileria antigen in vaccinated animals. In addition, TNF-α is the principle cytokine in modulating the cytotoxic activity of cytotoxic T-lymphocytes (CTL). Immunological analysis of the vaccine was performed by using two cell mediated immunity (CMI) in vitro and in vivo DTH test (Theilerin) and TNF-α assay. RESULTS: The results of immune responses of susceptible immunized cattle by bioreactor vaccine in comparison with conventional flask vaccine revealed a significant stimulation of immune cells by transcription of high level of TNF-α and positive reaction against Theileria antigen in Theilerin skin test (DTH). CONCLUSION: The equal immunological results achieved in both above mentioned vaccines verified the satisfactory immunity for aerobic bioreactor theileriosis vaccine for advance mass vaccination in the field on a large-scale.

Scientometric analysis and mapping of scientific articles on Behcet's disease.

BACKGROUND: Behçet's disease (BD) is a systemic vasculitis disease with oral and genital aphthous ulceration, uveitis, skin manifestations, arthritis and neurological involvement. Many investigators have published articles on BD in the last two decades since introduction of diagnosis criteria by the International Study Group for Behçet's Disease in 1990. However, there is no scientometric analysis available for this increasing amount of literature. METHODS: A scientometric analysis method was used to achieve a view of scientific articles about BD which were published between 1990 and 2010, by data retrieving from ISI Web of Science. The specific features such as publication year, language of article, geographical distribution, main journal in this field, institutional affiliation and citation characteristics were retrieved and analyzed. International collaboration was analyzed using Intcoll and Pajek softwares. RESULTS: There was a growing trend in the number of BD articles from 1990 to 2010. The number of citations to BD literature also increased around 5.5-fold in this period. The countries found to have the highest output were Turkey, Japan, the USA and England; the first two universities were from Turkey. Most of the top 10 journals publishing BD articles were in the field of rheumatology, consistent with the subject areas of the articles. There was a correlation between the citations per paper and the impact factor of the publishing journal. CONCLUSION: This is the first scientometric analysis of BD, showing the scientometric characteristics of ISI publications on BD.

An overview and mapping of childhood tuberculosis: prevalence, scientific production and citation analysis.

AIM: The study aimed to analyze publications in the field of "pediatric tuberculosis" and associate them with regional Tuberculosis (TB) profile. METHODS: A schematic analysis of scientific production in the field of pediatric tuberculosis between 1990 and 2010 using ISI web of science was carried out. Terms used for searches were each as a combination of "Mycobacterium Tuberculosis", or "Tuberculos*" and "Child", or "Infant", or "New born", or "Neonatal", or "Adolescent", or "Pediatric". Features including year of publication, citation per year, country of origin, funding state, contributing university, language, leading journals and authors, and highly cited articles, main journal publishing these articles were taken into account. RESULTS: The search retrieved 3417 articles (of 4559 total) with an almost gradual annually progressive pattern from 20 (in 1990) to 302 (in 2009) which have been cited totally 48459 times and 14.18 times per article. The greatest contribution originated from United States of America (25.11%) followed by South Africa (12.17%), and England (11.18%). Interestingly, 82.4% of all South African articles were from Stellenbosch University and Cape Town University on contrary. CONCLUSIONS: International Journal of Tuberculosis and Lung Disease ranked as the first with regard to the number of articles and Lancet with regard to the number of highly cited articles. Developing countries excluding South Africa despite their high prevalence scarcely contribute to the field and USA is the leading country in the field.

A scientometric analysis of 20 years of research on breast reconstruction surgery: a guide for research design and journal selection.

BACKGROUND: Breast reconstruction refers to the rebuilding of a woman's breast using autologous tissue or prosthetic material to form a natural-looking breast. It is increasingly offered to women undergoing mastectomy for breast cancer. However, there is no systematic analysis available for the expanding area of research on breast reconstruction. METHODS: A bibliometric method was used to obtain a view of the scientific production about breast reconstruction by data extracted from the Institute for Scientific Information (ISI). Specific parameters were retrieved from the ISI. Articles about breast reconstruction were analyzed to obtain a view of the topic's structure, history, and document relationships using HistCite software. Trends in the most influential publications and authors were analyzed. RESULTS: The number of articles was constantly increasing. Most highly cited articles described the methods of flap construction in the surgery. Other highly cited articles discussed the psychological or emotional aspects of breast reconstruction, skin sparing mastectomy, and breast reconstruction in the irradiated breast. CONCLUSIONS: This was the first breast reconstruction scientometric analysis, representing the characteristics of papers and the trends of scientific production. A constant increase in the number of breast reconstruction papers and also the increasing number of citations shows that there is an increasing interest in this area of medical science. It seems that most of the research in this field is focused on the technical aspects of surgery.

Presentation of psoriatic arthritis in the literature: a twenty-year bibliometric evaluation.

Psoriatic arthritis is an inflammatory arthritis disabling patients with psoriasis. Bibliometric studies are tools for evaluating scientific productions in different countries, universities as well as publications related to a special topic. We aimed to perform a scientometric study to evaluate articles published under "Psoriatic arthritis" topic and also attempted to compare publications of different authors, countries, universities, and journals related to this topic. Study was performed on all articles published between 1989 and 2009. The ISI web of science was our main source. Two key words, "Psoriatic arthritis" and "Psoriatic arthropathy," were used to conduct search. Original articles were subject of further evaluation. A whole number of 3,727 article was result of our search. From this number, 1,961 (52.6 %) were original articles. Whole original articles were cited 38,613 times with average citations per item of 19.69. Gladman DD was the most popular author in this field. Articles were mostly in English (91.3 %). USA was the leading country in producing article under this topic with 463 (23.6 %) publications. University of Toronto was the first rank institution while publishing 125 (6.4 %) articles. More than half of articles were published under "Rheumatology" subject. "Journal of Rheumatology," "Annals of the Rheumatic Diseases," and "Arthritis and Rheumatism" were three journals with highest number of articles on this topic. There has been growing interest in psoriatic arthritis subject during these two decades. Between countries, institutions and journals; USA, university of Toronto, "Journal of Rheumatology," "Annals of The Rheumatic Diseases," and "Arthritis and Rheumatism" have special contributions to body of literature published under this topic, respectively.

Methadone maintenance therapy outcomes in Iran.

INTRODUCTION: Because of the increasing number of injecting drug users (IDUs) in Iran and the risk of the spread of HIV infection, harm reduction programs have been considered for conventional law enforcement measures. The aim of this study was to evaluate the efficacy of methadone maintenance therapy (MMT) in IDUs and the associated health and social outcomes. MATERIAL AND METHODS: This case-control study was conducted at the Persepolis Harm Reduction Center in Tehran during the year 2006. Data were gathered from two groups of randomly chosen patients. The first group consisted of 75 IDU patients who had undergone at least 6 months of methadone treatment (the MMT group), and second group consisted of 75 newly admitted clients (the control group). Participants were assessed on their dangerous injection and sexual behaviors, social well-being, and patterns of drug use. The results were compared between the two groups. RESULTS: The mean age of participants in the two groups was almost the same (34.28 years in the control group and 35.68 years in the MMT group, p >.05). Prevalence of drug injection in the MMT group was less than that in the control group (16% vs. 100%). There was also a dramatic difference in needle and syringe sharing (40% in the control group vs. 4% in the MMT group) but not in crimes and arrests (p = .4). Those in the MMT group had a better relationship with their families, partners, coworkers, and neighbors compared with controls. There was no considerable difference in dangerous sexual behaviors between the two groups. CONCLUSIONS: Given the large number of HIV-positive cases among IDUs and considering that injection drug use is the main spreading factor for HIV, MMT would play a major role in controlling the HIV epidemic through reduction of heroin injection and the risk behaviors related to it. High inflation rate, lack of interorganization coordination, budget limitation, and no follow-up were the most important limitations of this study.

Therapeutic effects of HESA-A in patients with end-stage metastatic cancers.

BACKGROUND: After cardiovascular disease, cancer is the most common cause of death. HESA-A is a natural product of herbal and marine origin. The aim of this study was to investigate the beneficial effects of HESA-A in patients with end-stage metastatic cancers. METHODS: In this clinical trial, 30 consecutive patients (18 men, 12 women) with end-stage cancers and liver metastasis at the Cancer Research Center of Tehran University of Medical Sciences were studied. Patients received HESA-A 50 mg/kg/d orally in 2 to 3 divided doses for 3 months. At the start and end of the 1st, 4th, 8th, and 12th weeks of the study, the patients were assessed and hematological and hepatic biochemical indices were measured. Also, the Karnofsky Performance Scale questionnaire was completed for each patient. RESULTS: The mean age of patients was 56.23 +/- 12.10 years. Mean Karnofsky Performance Scale scores of the patients increased from 48 +/- 14.36 to 78.42 +/- 15.37 after 12 weeks of treatment. A total of 90.4% of the patients who remained in the study were alive for 12 weeks. No significant hepatic or hematologic adverse effect was seen during the study. CONCLUSION: HESA-A appears to be an effective and safe anticancer compound that may increase survival of end-stage patients and can be used in selected cases. Further prospective controlled clinical trials with large sample size and longer follow-up period are warranted to understand the mechanisms of action of HESA-A and evaluate its long-term effects on the survival and quality of life of patients with cancer and as well as its unfavorable side effects.