A review of heavy metals pollution in riverine sediment from various Asian and European countries: Distribution, sources, and environmental risk.

Riverine sediments are important reservoirs of heavy metals, representing both historical and contemporary anthropogenic activity within the watershed. This review has been conducted to examine the distribution of heavy metals in the surface sediment of 52 riverine systems from various Asian and European countries, as well as to determine their sources and environmental risks. The results revealed significant variability in heavy metal contamination in the world's riverine systems, with certain hotspots exhibiting concentrations that exceeded the permissible limits set by environmental quality standards. Among the studied countries, India has the highest levels of chromium (Cr), cobalt (Co), manganese (Mn), nickel (Ni), zinc (Zn), cadmium (Cd), copper (Cu), and lead (Pb) contamination in its riverine systems, followed by Iran > Turkey > Spain > Vietnam > Pakistan > Malaysia > Taiwan > China > Nigeria > Bangladesh > Japan. Heavy metal pollution in the world's riverine systems was quantified using pollution evaluation indices. The Contamination Factor (CF) revealed moderate contamination (1 ≤ CF < 3) throughout the geological units, with the exception of Pb, Cd, and Cu. The Contamination Degree (CD) classifies the contamination level into different categories: Low degree of contamination (CD < 6), moderate degree of contamination (6 ≤ CD < 12), considerable degree of contamination (12 ≤ CD < 24), and a very high degree of contamination (CD ≥ 24), while the Pollution Load Index (PLI) estimate the total amount of heavy metal pollution in riverine sediments, with Turkey having the highest PLI value of 6.512, followed by Spain, Vietnam, Taiwan, Pakistan, Bangladesh, China, India, Japan, Malaysia, Iran, and Nigeria. In applied multivariate statistics, correlation analysis determined the fate and distribution of heavy metals in riverine systems, while Principal Component Analysis (PCA) elucidated the potential sources, including industrial, agrochemical, mining, and domestic wastewater discharges, lubricant leakages, multiple geogenic inputs, erosion of mafic and ultramafic rocks, and minimal atmospheric deposition. As per Potential Ecological Risk Index (PERI) perspectives, Vietnam, Spain, and Turkey have the highest ecological risk, followed by Nigeria > Pakistan > Bangladesh > China > Taiwan > Japan and Iron, while the potential risks of ∑non-carcinogenic Pb, Cr, Ni, Cu, Cd, Co, Zn, and Mn for exposed human children and adults through ingestion and dermal contact were significantly influenced between acceptable to high risk, necessitating special attention from pollution control agencies.

Spatial distribution and health risks assessment of heavy metals in e-waste dumping sites from Pakistan.

The present study focused on to determine the concentration and health risk of heavy metals (Cu, Pb, Zn, Cd, Hg, Cr) in e-waste contaminated soils collected from different provinces of Pakistan. Further, the impact of heavy metals on soil enzyme activities and microbial community was also investigated. The concentration (mg/kg) of Hg, Zn, Fe, Cu, Pb, Cd, and Cr ranged between 0-0.258, 2.284-6.587, 3.005-40.72, 8.67-36.88, 12.05-35.03, 1.03-2.43, and 33.13-60.05, respectively. The results revealed that Lahore site of Punjab province indicated more concentration of heavy metals as compared to other sites. The level of Cr at all sites whereas Hg at only two sites exceeds the World Health Organization standards (WHO) for soil. Soil enzyme activity exhibited dynamic trend among the sites. Maximum enzyme activity was observed for urease followed by phosphatase and catalase. Contamination factor (Cf), Pollution load index (PLI), and geo-accumulation index (Igeo) results showed that all the sites are highly contaminated with Cu, Cd, and Pb. Hazard index (HI) was less than 1 for children and adults suggesting non-carcinogenic health risk. Principle component analysis results depicted relation among Cr, Fr, catalase, and actinomycetes; Cd, OM, urease, and bacteria, and Pb, Cu, Zn, Hg, and phosphatase, suggesting soil enzymes and microbial community profiles were influenced by e-waste pollution. Therefore, there is a dire need to introduce sustainable e-waste recycling techniques as well as to make stringent e-waste management policies to reduce further environmental contamination.

Population exposure to emerging perfluoroalkyl acids (PFAAs) via drinking water resources: Application of multivariate statistics and risk assessment models.

This study assessed the occurrence, origins, and potential risks of emerging perfluoroalkyl acids (PFAAs) for the first time in drinking water resources of Khyber Pakhtunkhwa, Pakistan. In total, 13 perfluoroalkyl carboxylic acids (PFCAs) with carbon (C) chains C4-C18 and 4 perfluoroalkyl sulfonates (PFSAs) with C chains C4-C10 were tested in both surface and ground drinking water samples using a high-performance liquid chromatography system (HPLC) equipped with an Agilent 6460 Triple Quadrupole liquid chromatography-mass spectrometry (LC-MS) system. The concentrations of ∑PFCAs, ∑PFSAs, and ∑PFAAs in drinking water ranged from 1.46 to 72.85, 0.30-8.03, and 1.76-80.88 ng/L, respectively. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluoropentanoic acid (PFPeA) were the dominant analytes in surface water followed by ground water, while the concentration of perfluorobutane sulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) were greater than long-chain PFOA and PFOS. The correlation statistics, which showed a strong correlation (p < 0.05) between the PFAA analytes, potentially indicated the fate of PFAAs in the area's drinking water sources, whereas the hierarchical cluster analysis (HCA) and principal component analysis (PCA) statistics identified industrial, domestic, agricultural, and commercial applications as potential point and non-point sources of PFAA contamination in the area. From risk perspectives, the overall PFAA toxicity in water resources was within the ecological health risk thresholds, where for the human population the hazard quotient (HQ) values of individual PFAAs were < 1, indicating no risk from the drinking water sources; however, the hazard index (HI) from the ∑PFAAs should not be underestimated, as it may significantly result in potential chronic toxicity to exposed adults, followed by children.

Nano round polycrystalline adsorbent of chicken bones origin for Congo red dye adsorption.

Nano round polycrystalline adsorbent (NRPA) of chicken bones origin was utilize as effective adsorbent in Congo red dye removal via aqueous media. The NRPA adsorbent was prepared via thermal decomposition and its structure was investigated with the aids of Transmission Electron Microscopy, Fourier Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy, Energy Dispersive X-ray Analysis (EDX), and X-ray Diffractometer (XRD). A monophasic apatite phase was confirmed from XRD investigation, while functional groups analysis showed that NRPA possessed CO32-, PO43- and OH- absorption bands. The maximum adsorption capacities derived from Langmuir isotherm is 98.216 mg g-1. From the combined values of n from Freundlich and separation factor (RL) of Langmuir models, the adsorption of CR by NRPA is favourable. Thermodynamic values of 5.280 kJ mol-1 and 16.403 kJ mol-1 K-1 were found for ΔH° and ΔS° respectively. The entire values of ΔG° which ranges from - 35.248 to - 459.68 kJ mol-1 were all negative at different temperatures. Thus, nano polycrystalline adsorbent of chicken bone origin can serve as excellent adsorbent in Congo red dye removal from waste water.

Bioactivity properties of hydroxyapatite/clay nanocomposites.

The need for bioactive and non-toxic biomaterials is on a high demand in tissue engineering applications nowadays. Hydroxyapatite (HAp) is the chief constituent of teeth and bones in mammas. One of the major challenges with the use of HAp in engineering application is its brittleness and to overcome this, it's important to react it with a material that can enhanced it's fragility. To this end, HAp and HAp/clay nanocomposites were developed via wet chemical process to mimic natural HAp and to equally confer special properties such as mechanical properties, high surface area, crystallinity, high porosity, and biocompatibility on the biomaterial. The functional groups properties of the as-prepared nanocomposites analyzed by FT-IR showed that the HAp and clay posed reactive centers such as Al-Al-OH, Si-Si-OH, Si-O, PO43-, -OH, and Si-O-Al. The XRD results confirmed the formation of HAp/clay nanocomposite, while SEM and TEM images showed the morphologies of the prepared nanocomposites to be round shape particles. Besides, EDX result revealed the Ca/P ratio of HAp and HAp-C to be lower than that of stoichiometric ratio (1.67) which implies the presence of K, Na, Ca, Mg, Si and Al in the HAp/clay nanocomposite. The mechanical properties of the apatite were greatly enhanced by the addition of clay. The physiological behaviour of the fabricated apatite composites in saline solution showed steady increase in the values of the saline pH of the various biomolecules until day 5 and became fairly constant at day 7 with pH range of 7.30-7.38. Though the saline solution was acidic at the beginning due to dissolved carbon dioxide, the pH of the saline solution containing the nanocomposites gradually became neutral and fairly alkaline over time as a result of the presence of Lewis basis structures in the composites which helps in neutralizing the acidic solution. Furthermore, proliferation of apatites particles onto the surface of the nanocomposites was observed after treatment with simulated body fluids (SBF) media for 7 days. Thus, HAp/clay nanocomposites can be useful biomaterials in bone tissue engineering.

Heavy metals in five commonly consumed fish species from River Swat, Pakistan, and their implications for human health using multiple risk assessment approaches.

This study analyzed the levels of heavy metals bioaccumulation in commonly consumed riverine fish species, including G. cavia, T. macrolepis, G. gotyla, S. plagiostomus, and M. armatus from River Swat in Pakistan, and quantify their potential risk to children and adults in general and fisherfolk communities using multiple pollution and risk assessment approaches. The highest metal detected by inductive coupled plasma mass spectrometry (ICP-MS) was Zn, which ranged from 49.61 to 116.83 mg/kg, followed by Fe (19.25-101.33 mg/kg) > Mn (5.25-40.35 mg/kg) > Cr (3.05-14.59 mg/kg) > Ni (4.26-11.80 mg/kg) > Al (1.59-12.25 mg/kg) > Cu (1.24-8.59 mg/kg) > Pb (0.29-1.95 mg/kg) > Co (0.08-0.46 mg/kg) > Cd (0.01-0.29 mg/kg), demonstrating consistent fluctuation with the safe recommendations of global regulatory bodies. The average bioaccumulation factor (BAF) values in the examined fish species were high (BAF > 5000) for Pb, Zn, Mn, Cu, Cr, Ni, and Cd, bioaccumulate (1000 > BAF < 5000) for Co, and probable accumulative (BAF <1000) for Fe, and Al, while the overall ∑heavy metals pollution index (MPI) values were greater than one (MPI > 1) indicating sever heavy metals toxicity in G. cavia, followed by S. plagiostomus, M. armatus, G. gotyla, and T. macrolepis. The multivariate Pearson's correlation analysis identified the correlation coefficients between heavy metal pairs (NiCr, CuCr, PbCr, AlCo, CuNi, and PbNi), the hierarchical cluster analysis (CA) determined the origin by categorizing heavy metal accumulation into Cluster-A, Cluster-B, and Cluster-C, and the principal component analysis (PCA) discerned nearby weathering, mining, industrial, municipal, and agricultural activities as the potential sources of heavy metals bioaccumulation in riverine fish. As per human risk perspective, S.plagiostomus contributed significantly to the estimated daily intake (EDI) of heavy metals, followed by G.cavia > M.armatus > G.gotyla > T.macrolepis in dependent children and adults of the fisherfolk followed by the general population. The non-carcinogenic target hazard quotient (THQ) and hazard index (HI) values for heavy metal intake through fish exposure were < 1, while the carcinogenic risk (CR) for individual metal intake and the total carcinogenic risk (TCR) for cumulative Cr, Cd, and Pb intake were within the risk threshold of 10-6-10-4, suggesting an acceptable to high non-carcinogenic and carcinogenic risk for both children and adults in the fisherfolk, followed by the general population.

New and legacy pesticidal persistent organic pollutants in the agricultural region of the Sultanate of Oman.

Comprehensive air and surface soil monitoring was conducted for new and legacy organochlorine pesticides (OCPs) to fill the knowledge and data gap on the sources and fate of pesticidal persistent organic pollutants (POPs) in the Sultanate of Oman. DDTs in agricultural soil samples ranged from 0.013 to 95.80 ng/g (mean: 8.4 ± 25.06 ng/g), with a median value of 0.07 ng/g. The highest concentration was observed at Shinas, where intensive agricultural practice is prevalent. The dominance of p,p'-DDT in soil and air reflected technical DDT formulation usage in Oman. Among newly enlisted POPs, pentachlorobenzene had the maximum detection frequency in air (47%) and soil (41%). Over 90% of sites reflected extensive past use of hexachlorobenzene. Major OCP isomers and metabolites showed net volatilisation from the agricultural soil, thereby indicating concurrent emission and re-emission processes from the soil of Oman. However, the cleansing effect of oceanic air mass is the possible reason for relatively lower atmospheric OCP levels from a previous study. Although DDT displayed maximum cancer risk, the level is below the permissible limit. DDT primarily stemmed from obsolete stock and inadequate management practices. Hence, we suggest there is a need for DDT regulation in Oman.

Deoxygenation turns the coastal Red Sea lagoons into sources of nitrous oxide.

Direct measurements of dissolved N2O concentrations, fluxes and saturation percentages undertaken for the first time in two coastal lagoons - Al-Shabab and Al-Arbaeen, along the east coast of the Red Sea, revealed the region as a significant source of N2O to the atmosphere. The exacerbated dissolved inorganic nitrogen (DIN) from various anthropogenic sources led to substantial oxygen depletion in both the lagoons, which turned to bottom anoxia at Al-Arbaeen lagoon during the spring season. We assume that the accumulation of N2O is caused by nitrifier-denitrification in the hypoxic/anoxic boundaries. In fact, the results indicated that oxygen-depleted bottom waters favoured denitrification when the oxygenated surface waters recorded nitrification signals. Overall, the N2O concentration ranged from 109.4 to 788.6 nM (40.6-325.6 nM) in spring and 58.7 to 209.8 nM (35.8-89.9 nM) in winter in the Al-Arbaeen (Al-Shabab) lagoon. The N2O flux ranged from 647.1 to 1763.2 µmol m-2 day-1 (85.9 to 160.2 µmol m-2 day-1) and 112.5 to 150.8 µmol m-2 day-1 (76.1 to 88.7 µmol m-2 day-1) in the spring and winter respectively, in the Al-Arbaeen (Al-Shabab) lagoons. The ongoing developmental activities may worsen the current situation of hypoxia and associated biogeochemical feedbacks; therefore, the present results underline the need for continuous monitoring of both lagoons to restrict more severe oxygen depletion in future.

PD-L1 and PD-L2 expression in colorectal cancer.

Context: The programmed death-1 (PD-1) is an immune checkpoint molecule that suppresses T-cell response. The binding of PD-1 to PD-L1/PD-L2 results cytokine production, and T-cell proliferation are reduced. Tumors expressing PD-L1 and PD-L2 escape from cytotoxic T-cells and are exposed to tumor progression. For this reason, immunotherapy has become a new option in the treatment of cancer. Aims: In this study, we examined the PD-L1 and PD-L2 expression in colorectal carcinoma (CRC), and evaluated the relationship between clinicopathological parameters and CD8+ T cells. Methods and Material: We evaluated CD8 expression in tumor-infiltrating lymphocytes and surrounding tumor lymphocytes with PD-L1, PD-L2 staining in tumor cells and immune cells formalin-fixed paraffin embedded samples of 124 patient diagnosed with CRC. Statistical Analysis Used: Pearson Chi-Square, Fisher Exact Chi-Square, and Pearson Exact Chi-Square analyses were used in the analysis of the cross tables. Survival distributions predicted Kaplan--Meier method and it was evaluated using log-rank statistics. Results: In our study, a significant correlation was found between PD-L1 expression and female sex and tumors with medullary morphology. No expression of PD-L2 was observed in tumors containing medullary morphology, and a statistically inverse relationship was observed between PD-L2 and the medullary component. PD-L1 positive tumor-infiltrating lymphocytes were determined to be an important predictor for recurrence-free survival. Conclusions: We believe that the evaluation of these parameters may be useful in the selection of patients who will benefit from immunotherapy in CRC cases.

The self-assessment of newly graduated orthopedic surgeons on essential surgical procedures.

OBJECTIVE: The aim of this study was to assess the self-confidence of newly graduated orthopedic surgeons on performing essential surgi- cal procedures. METHODS: The study included 151 orthopedics and traumatology surgeons who had completed their (orthopedics and traumatology) training within the last year. They were asked to complete an online questionnaire which was available from February 2020 to May 2021. In the questionnaire, newly graduated orthopedic surgeons were asked whether they could do the 18 listed essential adult and 8 listed essential pediatric cases independently. They were asked about patient follow-up systems and who these were supervised by, the demo- graphic data of the city and about the institution they were trained in, and how many times they performed the listed surgeries during their training. RESULTS: 74 (49%) of the participants received their training in training and research hospitals, 69 (45.7%) in state university hospitals, and 8 (5.3%) in foundation university hospitals. More than 80% of the participants answered, "I can do it independently" for 13 (81.6%) out of 16 adult cases and 7 (87.5%) out of 8 paediatric cases. The average self-efficacy score of the participants was 32.22 out of 36 for adult cases and 15.3 out of 16 for paediatric cases. The total average self-efficacy score was 47.52 out of 52. CONCLUSION: This study has shown us that newly graduated orthopedic surgeons have the self-confidence to handle many of the essential types of cases independently.

The effect of different treatment modalities on survival in elderly patients with locally advanced non-small cell lung cancer.

PURPOSE: The aim of this study is to investigate the effect of treatment modalities on survival among unoperat ed and locally-advanced non-small cell lung cancer (NSCLC) patients aged 70 years and older, representing real-life data. METHODS: From 2005 through 2017, medical records of 2259 patients with lung cancer from Okmeydani Training and Research Hospital-Istanbul/Turkey were reviewed retrospectively. Patients with locally advanced NSCLC ≥ 70 years of age who did not undergo surgery for lung cancer were reviewed. In total, 130 patients were eligible for the final analysis. Patients were stratified into four groups as: chemotherapy (CT), concurrent chemoradiotherapy (cCRT), sequential chemoradiotherapy (sCRT), and radiotherapy (RT) only. RESULTS: Of the 130 patients included in the analysis; CT, cCRT, sCRT, and RT only were applied to 25(19.2%), 30(23.1%), 31(23.8%), and 44(33.8%) patients, retrospectively. Twelve (9.2%) patients were female. Median age was 72 years (range, 70-88). Sixty (46.2%) patients had stage IIIA disease and 70(53.8%) patients had stage IIIB disease. Median progression-free survival(mPFS) in patients treated with CT, cCRT, sCRT, and RT were 8.0, 15, 10, and 9.0 months, respectively(p = 0.07). Corresponding median overall survival (mOS) were 10, 33, 20, and 15 months (p = 0.04). In multivariate analysis, stage IIIB disease [hazard ratio (HR), 2.8], ECOG-PS 2(HR, 2.10), and ECOG-PS 3-4(HR, 5.13) were found to be the negative factors affecting survival, while cCRT (HR, 0.45) and sCRT (HR, 0.50) were the independent factors associated with better survival. CONCLUSION: This study showed that the use of combined treatment modality was associated with better survival in elderly patients with locally advanced NSCLC, with the greatest survival observed in patients treated with cCRT. We therefore suggest that cCRT, when feasible, should be strongly considered in locally advanced NSCLC patients 70 years and over.

Effects of ceranib-2 on cell survival and TNF-alpha in colon cancer cell line.

OBJECTIVE: The aim of this study was to investigate the effects of a novel anti-cancer drug, ceranib-2, which targets the acid ceramidase, in human colon cancer cell line. MATERIALS AND METHODS: The cell lines were treated with 50 µM of ceranib-2. Relative mRNA expression of TNF-alpha, TNF-R1 and ASAH were assessed by quantitative RT-PCR. RESULTS: Ceranib-2 reduced cell viability in a dose-dependent manner and the apoptotic values of cells following treatment with the dose of 50 µM were reduced significantly both at 24 h and 48 h compared to the control cells (p < 0.001). TNF-alpha receptor 1 (TNF-R1) mRNA levels were reduced significantly in the cell lines treated with both 25 µM and 50 µM of ceranib-2 for 24 h compared to the control cells (p < 0.05), whereas the difference between the treatment and the control cell lines diminished at 48 h. The human acid ceramidase gene (ASAH) mRNA levels were significantly higher in the cell lines treated with 50 µM of ceranib-2 for 48 h than in the other cell lines (p < 0.001). CONCLUSION: The study shows that ceranib-2 increased apoptosis by inducing ASAH expression and reduced TNF-R1 expression in human colon cancer cell lines in a dose and time-dependent manner (Fig. 3, Ref. 17).

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis

PURPOSE: Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment. METHODS: We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers. RESULTS: Median age of group was 58. 82 % had an ECOG PS of 0-1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate. CONCLUSION: Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate (AU)

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis.

PURPOSE: Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment. METHODS: We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers. RESULTS: Median age of group was 58. 82 % had an ECOG PS of 0-1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate. CONCLUSION: Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate.

Effects of doxycycline on renal ischemia reperfusion injury induced by abdominal compartment syndrome.

BACKGROUND: The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1ß, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS: Creatinine, MDA, IL-1ß, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1ß, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION: Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Combined thrombophilic factors increase the risk of recurrent thrombotic events in Behcet's disease.

This retrospective study aims to seek a relationship between the number of thrombotic events and presence of thrombophilic factors in Behcet's disease (BD). Any patient with a vascular problem evaluated for at least one thrombophilic factor was deemed eligible for the present study. Upon an evaluation of their medical records, 96 (23.9%) of the 402 patients diagnosed with BD were determined to have a history of thrombosis. Of these 96 patients, 72 (75%) had only one thrombotic attack, while the remaining 24 (25%) had two or more thrombotic attacks. Thrombophilic parameters were evaluated in only 36 of the 72 patients (50%) who had one thrombotic event (Group I) and in 18 of the 24 patients (75%) who had more than one thrombotic event (Group II). The patients with recurrent thrombotic events had a significantly higher incidence of combined thrombophilias than those patients with only one thrombotic event (8/18, 44%; 4/36, 11%; p < 0.01). The number of the patients free from thrombophilic risk factors was significantly higher in Group I than in Group II (21/36, 58%; 4/18, 22%; p < 0.02). Group II had an increased frequency of combined thrombophilic risk factors (OR 6.4; 95% CI 1.5-25.8) when compared to Group I. No significant differences were found between Groups I and II with respect to clinical features of BD. In conclusion, combined thrombophilias in patients with BD may have a role in the development of recurrent thrombotic events.

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and ß-cell lymphoma 2 (ßcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1ß, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of ßcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.