Health risk assessment of heavy metal toxicity in the aquatic environment of the Persian Gulf.

This study aims to explore the potential health risks linked to four heavy metals/metalloids (Pb, Cd, As, Hg) present in four commercially important fish species (Scombromorus commerson, Pseudorhombus elevatus, Thunnus tonggol and Otolithes ruber) in the Persian Gulf. Metals in fish muscle tissue were analyzed via ICP-MS. The analysis revealed that Scombromorus commerson (except for Pb) and Thunnus tonggol (except for As) exhibited the highest and lowest contamination levels, respectively. The Hazard Index findings highlighted arsenic and mercury as the most hazardous elements. However, the Target Hazard Quotient values for each metal and fish species remained within safe thresholds. The highest and lowest Total Carcinogenic Risk was concerning Pseudorhombus elevates (As: 7.41-E05), and Thunnus thonggol (Pb: 3.21-E07), respectively. TCR analysis suggests that the cancer risk of studied metals was below the negligible level (TCR < 10-6) or within the acceptable level (10-6 < TCR < 10-4), potentially not posing carcinogenic risks through extended consumption.

Evaluation of short-term adverse events of COVID-19 vaccines: An observational study.

Coronavirus disease 2019 (COVID-19) vaccines are the most effective tools in managing the pandemic. However, the concern about these vaccines is the occurrence of unwanted adverse events (AEs). This study aimed to evaluate the short-term AEs of COVID-19 vaccines (Sputnik V, Astrazenka, and Sinopharm). A cross-sectional study using an online questionnaire was conducted among 321 vaccinated individuals. Demographic information, history of drug use, prior infection with COVID-19, the type of vaccine, vaccination stage, local injection site complication, systemic complication, and allergic reactions were collected and evaluated. Local complications, including pain and swelling at the injection site, and systemic complications, including fever, fatigue, lethargy, lymphadenopathy, and diarrhea, were reported after the injection of the AstraZeneca vaccine was more than the other 2 vaccines; The prevalence of fatigue and lethargy was higher than other systemic complications. The least reported complication was due to lymphadenopathy. The Sinopharm vaccine showed a lower prevalence of AEs than the other 2. The rare AEs, such as facial paralysis, nasal bleeding, and urticarial, were further reported after injection of the AstraZeneca vaccine. In general, the severity of systemic complications after the second dose of the vaccine was also higher than the first dose. All 3 vaccines were safe and tolerable. The most commonly reported AEs were injection site pain (local) and fatigue and lethargy (systemic). These expected AEs occurred shortly after vaccination and indicated an early immune response after vaccination.

Efficacy and safety of licorice (Glycyrrhiza glabra) in moderately ill patients with COVID-19: a randomized controlled trial.

Licorice extract (glycyrrhizin), a potent antiviral, anti-inflammatory, and antioxidant remedy, is a potential therapeutic option for COVID-19. We evaluated the efficacy and safety of licorice in patients with moderate COVID-19. In this study, 60 patients with confirmed COVID-19 were randomly assigned in a 1:1 ratio to receive licorice (at a dose of 760 mg three times a day for seven days) or control groups. The primary outcomes were SPO2, body temperature, and respiratory rate (RR) after the end of the intervention. The findings indicated that SPO2, body temperature, and RR had no significant difference between the groups at the end of the intervention. However, CRP and ALT improved in the licorice group toward the baseline. The number of patients with worse prognoses, LOS, mortality, and the incidence of adverse events were not different between the groups at the end of the study. Licorice had no beneficial effect on the clinical symptoms of COVID-19. Moreover, this intervention demonstrated a safe profile of adverse events. The confirmation of the results of this preparatory trial requires more detailed multiple-center trials with a larger sample size.

Arsenic trioxide-induced cytotoxicity in A549 cells: The role of necroptosis.

INTRODUCTION: Lung cancer is one of the deadliest cancers globally. Arsenic trioxide (ATO) is still present as a highly effective drug in treating acute promyelocytic leukemia (APL). Chemotherapy resistance is one of the major problems in cancer therapy. Necroptosis, can overcomes resistance to apoptosis, and can promote cancer treatment. This study examines the necroptosis pathway in A549 cancer cells exposed to ATO. METHODS: We used the MTT test to determine the ATO effects on the viability of A549 cells at three different time intervals. Also, the reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were performed in three-time intervals. The effect of ATO on apoptosis was evaluated by Annexin V / PI staining and, the RIPK1 and MLKL gene expression were measured by Real-Time PCR. RESULTS: The ATO has dose and time-dependent cytotoxic effects, so at 24, 48, and 72 h, the IC50 doses were 33.81 '11.44 '2.535 µM respectively. A 50 µM ATO is the most appropriate to increase the MMP loss significantly at all three times. At 24 and 48 h after exposure of cells to ATO, the ROS levels increased. The RIPK1 gene expression increased significantly compared to the control group at concentrations of 50 and 100 µM; however, MLKL gene expression decreased. CONCLUSIONS: The A549 cells, after 48 h exposure to ATO at 50 and 100 µM, induces apoptosis and necroptosis. Due to the reduced expression of MLKL, it can be concluded that ATO is probably effective in the metastatic stage of cancer cells.

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial.

Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27-18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34-4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13-17) in the melatonin group and 21 days (14-24) in the control group (OR; 5.00, 95% CI, 0.15-9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9-13) in the melatonin group and 16 days (10-19) in the control group (OR; 3.92, 95% CI, 1.69-6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia.

Evaluation of the effect of melatonin in patients with COVID-19-induced pneumonia admitted to the Intensive Care Unit: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N7 ". The registration date was February 16, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Effects of Ginger on clinical manifestations and paraclinical features of patients with Severe Acute Respiratory Syndrome due to COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We investigate the effects of Ginger, compared to the usual therapeutic regimen on clinical manifestations and paraclinical features in patients with confirmed COVID-19 that are moderately ill. TRIAL DESIGN: This is a single center, randomized, double-blind, placebo-controlled clinical trial with parallel group design. PARTICIPANTS: Inclusion criteria: 1. Patients admitted to Severe Acute Respiratory Syndrome (SARS) Departments at Shahid Mohammadi Hospital, Bandar Abbas, Iran 2. Age ≥18 years (weight ≥35 kg) 3. Hospitalized ≤48 hours 4. Confirmed SARS-CoV-2 diagnosis (Positive polymerase chain reaction (PCR)) 5. Moderate pneumonia and lung involvement in imaging 6. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm Exclusion criteria: 1. Underlying diseases, including heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders 2. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs 3. Severe and critical pneumonia 4. History of known allergy to Ginger 5. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19 along with Ginger-based herbal tablets (Vomigone ®, Dineh Pharmaceutical Company, Iran) at a dose of 1000 mg three times a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol, along with Vomigone-like placebo tablets (Dineh Pharmaceutical Company, Iran) at a dose of two tablets three times a day for a period of seven days. MAIN OUTCOMES: The primary outcome is recovery rate of clinical symptoms, including fever, dry cough, tiredness, and GI symptoms as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein within seven days of randomization. Time to improvement of clinical and paraclinical features along with the incidence of serious adverse events are the secondary outcomes within seven days of randomization. RANDOMIZATION: An interactive web-based system will be used to allocate eligible participants, based on the inclusion and exclusion criteria, to one of the two study arms (in a 1:1 ratio) using block randomization. BLINDING (MASKING): All study participants, research coordinators, clinicians, nurses, and investigators will be blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 84 participants will be randomized into two groups of 42 patients. TRIAL STATUS: The protocol is Version 1.0, May 23, 2020. Recruitment began July 21, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N1 ". Registration date is 23 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Effects of Licorice on clinical symptoms and laboratory signs in moderately ill patients with pneumonia from COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. INCLUSION CRITERIA: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. RANDOMIZATION: An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is "IRCT20200506047323N2", https://www.irct.ir/trial/47990 . The registration date is 31 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The Therapeutic Role of Carotenoids in Diabetic Retinopathy: A Systematic Review.

BACKGROUND: Carotenoids are a large group of natural pigments that occur in many foods, fruits, and vegetables. Several studies have shown a number of biological properties of carotenoids, particularly beneficial impacts on cancer, metabolic, neurodegenerative, and cardiovascular diseases. However, recent evidence has shown that these compounds could prevent, delay, and ameliorate diabetic retinopathy (DR). The aim of current study was to review the therapeutic effects of carotenoids in the treatment of DR and discuss the molecular mechanisms that are behind these pharmacological activities. METHODS: Six online databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, ScienceDirect, and ProQuest) were searched until September 2019. The systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. RESULTS: A total of 25 studies were included after the final retrieval. A relationship was observed between carotenoids and management of DR. Findings also demonstrated that the underlying mechanism of beneficial effects of these compounds was antioxidant, anti-inflammatory, anti-angiogenic, and neuroprotective properties. CONCLUSION: Carotenoids potentially delay the initiation and prevent the progression of DR; however, ample preclinical studies are required to confirm their effect, and adequate clinical trials are needed to really understand how well these compounds influence DR among humans.

An ethnobotanical survey on hormozgan province, Iran.

OBJECTIVE: The present study is based on an ethnobotanical research project conducted in Hormozgan province that is located in south of Iran, bordering waters of the Persian Gulf and Oman Sea. This survey was carried out in order to recover the ethnobotanical and ethnomedicinal knowledge of the residents of this province. They are using medicinal and functional plants for treating or preventing several diseases. MATERIALS AND METHODS: Ethnobotanical data sheets were run with the native inhabitants and people of the province by arranging frequent field trips to different parts of the province and direct interviews with them especially those who were more familiar with the plants and their usage. RESULTS: A total of 150 plant species belonging to 53 families were recorded for their ethnobotanical and ethnomedicinal uses among the people of province. The records were developed by scientific names, family names, local names, medicinal parts used, different ways of their application, and traditional uses of the plants. There was high compliance in the use of plants in painful disorders, gastrointestinal, and dermatological diseases. CONCLUSION: This study revealed that the people of Hormozgan province have a rich knowledge of natural resources. The use and consumption of medicinal plants are still important parts of their life. Rational use of native medicinal plants may benefit and improve their living standards and quality of life. The results of this study can be used as a basis for selecting herbs for further pharmacological, phytochemical, and pharmacognostical studies.

Development and application of an automated chromogenic thrombin generation assay that is sensitive to defects in the protein C pathway.

BACKGROUND: Activated protein C resistance (APCR) within a thrombin generation test (TGT) system is associated with an increased risk of venous thromboembolism (VTE). However, application of the TGT is restricted by the analytical platforms used to monitor thrombin generation. Using a routine coagulation analyser we have developed an automated chromogenic TGT that is sensitive to defects in the protein C pathway. METHOD: The TGT was performed on a TOP500 analyser, in the presence and absence of Protac. The reaction was monitored using a substrate with slow kinetics for thrombin (S-2444). Results were expressed as the area under the curve normalised ratio (AUCnr). Assay results were compared with Coatest APCR (expressed as APC-ratio [CoAPCr]). PATIENTS: Samples were obtained from 35 healthy subjects and 91 patients with previous history of VTE. Of these patients, 19, 17, and 9 had heterozygous factor V Leiden (FVL), antiphospholipid syndrome (APS), and protein C/protein S deficiencies (PC/PS) respectively. RESULTS: Inter-assay imprecision in the presence and absence of Protac were 20% and <5% respectively. There was a significant difference between the AUCnr of normals (median [IQR]: 2.8 [2.4-4.7]) compared to: FVL (1.0 [0.7-1.2]); PC/PS (1.1 [0.9-1.2]); and APS (1.1 [0.8-1.4]); p<0.001 for each comparison. No significant difference was seen between the AUCnr of normals and other VTE patients. The detection rate of AUCnr and CoAPCr were: 100% and 56% for FVL; 88% and 44% for PC/PS; and 64% and 45% for APS respectively. CONCLUSION: The automated TGT exhibited good sensitivity to defects in the protein C pathway.

A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study.

The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the protein C (PC) pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. The aim of this multicenter study involving three laboratories was to evaluate the test sensitivity to PC pathway abnormalities by retrospectively testing frozen plasma samples obtained in the different laboratories. Test results were significantly lower (p < 0.0001) in subjects who presented with any confirmed PC pathway abnormality than in those without. The cut-off value, defined in each participating center as the mean value minus one standard deviation of test results obtained in 30 normal samples, was found to provide a sensitivity-to-specificity ratio similar to that obtained using ROC-analysis. The assay performed well in carriers of the factor V Leiden mutation (n = 81), patients with PC deficiency (n = 40), combined defects (n = 55) or lupus anticoagulant (n = 44), with test results below the locally defined cut-off values in 97.5%, 95.0%, 100% and 100% of the tested subjects, respectively. The assay sensitivity for PS deficiency (n = 62) was 87.1%. Only 13.6% of the 272 subjects without any PC pathway abnormality had a decreased test result. So, using the locally defined cut-off values, the overall test sensitivity to all tested PC pathway abnormalities was 95.0% (95%CI = 91.8-97.3), its specificity 86.4% (95%CI = 81.8-90.2), its negative predictive value 94.4% (95%CI = 90.8-96.9) and its positive predictive value 87.9% (95%CI = 83.7-91.3).

Determination of gelatinase A using a modified indirect hemagglutination assay in human prostate cancer screening and assessment of its correlation with prostate-specific antigen parameters.

BACKGROUND: Prostate cancer is the most common malignancy affecting men and is a major cause of cancer death. There are increasing data on novel tumor markers, such as gelatinase A, which play a key role in tissue invasion and metastasis. OBJECTIVES: We designed a study to evaluate total gelatinase A content using a simple and applicable Indirect hemagglutination (IHA) test in harmony with gelatinase A activity in serum samples as compared with prostate-specifc antigen (PSA) parameters. METHODS: In this study, we analysed the circulating form of gelatinase A (MMP-2) in patients suffering from either benign prostate hyperplasia (n=54) or prostate cancer (n=26) versus normal individuals as control (n=26). The gelatinolytic activity was determined by zymography and total MMP-2 content was measured by a novel IHA method. Total PSA and free PSA were quantified using a standard ELISA technique. RESULTS: Correlation of densitometric analysis of gelatinase A activity and IHA titer is significant at the 0.01 level (P<0.01, rho=0.916). Correlation of PSA and IHA titer is significant at the 0.01 level (P<0.01, rho=0.746). Correlation of free PSA and IHA titer is significant at the 0.01 level (P<0.01, rho=0.749). Borderline of IHA titer in patients with prostate cancer was 512+/-1 tube titer, in benign prostate hyperplasia patients was 128+/-1 tube titer and the titer in normal individuals was 8+/-1 tube titer. CONCLUSIONS: These results demonstrate that assessment of gelatinase A might be a promising procedure for monitoring and screening patients with prostate cancer.

Inhibition of APC anticoagulant activity on oxidized phospholipid by anti-{beta}2-glycoprotein I monoclonal antibodies.

Activated protein C (APC) anticoagulant activity and the ability to be inhibited by auto-antibodies associated with thrombosis are strongly augmented by the presence of phosphatidylethanolamine (PE) and phospholipid oxidation. beta(2)-glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies present in patients with the antiphospholipid syndrome. We therefore investigated whether anti-beta(2)-GPI monoclonal antibodies (mAbs) could inhibit APC with similar membrane specificity. Five mouse mAbs that reacted with different epitopes on beta(2)-GPI were examined. Each inhibited the PE-, phospholipid oxidation-dependent enhancement of APC anticoagulant activity and required antibody divalency. A chimeric APC that retains anticoagulant activity but is relatively unaffected by protein S, PE, or oxidation was not inhibited by the antibodies. In purified systems, anti-beta(2)-GPI mAb inhibition of factor Va inactivation was greater in the presence of protein S and required beta(2)-GPI. Surprisingly, although the mAbs did increase beta(2)-GPI affinity for membranes, PE and oxidation had little influence on the affinity of the beta(2)-GPI antibody complex for the membrane vesicles. We conclude that antibodies to beta(2)-GPI inhibit APC function specifically and contribute to a hypercoaguable state by disrupting specific protein-protein interactions induced by oxidation of PE-containing membranes.

Cryptosporidium infection in diarrheic children in southeastern Iran.

In a cross-sectional study conducted in children referred to Bandar Abbas Pediatric Hospital in southeastern Iran, the prevalence of Cryptosporidium infection was 7%. Diarrhea lasted significantly longer in children infected with Cryptosporidium. There were also a significant association between Cryptosporidium infection and underweight children and no association with parent's occupation, breast-feeding, source of drinking water, vicinity or presence of sewage or animal exposure.

Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand.

Our previous study showed that in vitro susceptibility of Plasmodium vivax to chloroquine has significantly decreased in Thailand within the past two decades. Thus, the evaluation of alternative antimalarials for treatment of vivax malaria is needed. The aim of this study was to examine parasitological and clinical efficacy of an artemisinin derivative (artesunate) for the treatment of vivax malaria in patients who were admitted to the Bangkok Hospital for Tropical Diseases. We randomly allocated patients aged 12-56 years to receive 3.3mg/kg (adult dose 200 mg) on the first day, and for the next four days each patient was given 1.65 mg/kg orally (adult dose 100 mg), total dose = 600 mg. After the five-day course of artesunate, primaquine was given: a single oral dose of 15mg for 14 days. A total number of 42 patients received treatment. All participants were followed up for 28 days. In all the cases, both parasitemia and fever were resolved rapidly; the mean fever clearance time and parasite clearance time, 14.6 and 36.7 hours, respectively, showed that therapeutic response to artesunate was better than that of chloroquine. The 14-day cure rate was 100%, but reappearance of parasitemia was seen in two patients on days 21 and 25 following treatment, respectively. These two cases of failure rate should be considered as true relapse rather than recrudescence, since the relapse interval in Southeast Asian vivax malaria according to recent findings seems to be 3 weeks after start of treatment, if primaquine is not given or an inadequate amount is given. In conclusion, artesunate might be useful in treatment of vivax malaria, causing a good blood schizontocidal effect. However, to prevent emerging resistance it should never be used alone.