Tumor necrosis factor alpha in ulcerative colitis and diverticular disease associated colitis

Conventional treatment of moderate-severe ulcerative colitis (UC) has resulted in only a limited therapeutic benefit. Advancing knowledge of UC pathogenesis and recent advances in biotechnology have led to the development of biological agents that selectively target individual inflammatory pathways. In particular, the role of tumor necrosis factor alpha (TNF-alpha) in UC pathogenesis has been clarified by serological and immunohistochemical studies in humans and by experimental models. Clinical efficacy of anti-TNF-alpha therapy with infliximab has been assessed in two large controlled trials, showing a good compromise between therapeutic gain and safety. The aim of this review is to provide an insight into the role of TNF-alpha and anti-TNF-alpha therapy in patients with UC and diverticular disease associated colitis.     

The analgesic effect of Carum copticum extract and morphine on phasic pain in mice

Pain is a universal complaint, which needs further investigations for new pain relieving agents. Carum copticum (L.) Sprague ex Turrill is a plant in Umbelliferae family, which is mentioned to have some therapeutic effects on headache and joint pains in Iranian traditional literature, but there are not enough scientific reports to prove its effects on pain. So, we conducted to design an experimental clinical trial study to assess and compare the analgesic effect of ethanolic extract of Carum copticum fruit with morphine by using a tail-flick analgesiometer device. Our results indicate that the test drug produced significant increase in tail-flick latency (TFL) during 2h post-drug administration (p<0.05). The peak of the effect was observed at 45min after drug injection, which was comparable to that of 1mg/kg morphine (i.p.). Positive results in this type of analgesiometric test indicate that the antinociceptive action may be of the opoid type. The present study supports the claims of Iranian traditional medicine showing that Carum copticum extract possesses a clear-cut analgesic effect. However, further investigations are required to evaluate the efficacy and safety of this herbal medication in man.     

Pharmacological basis for the use of Borago officinalis in gastrointestinal, respiratory and cardiovascular disorders

AIM OF THE STUDY: In this study, we investigated the crude extract of Borago officinalis leaves (Bo.Cr) for its antispasmodic, bronchodilator, vasodilator and cardio-depressant activities to rationalize some of the traditional uses. MATERIALS AND METHODS: Bo.Cr was studied using different isolated tissue preparations including rabbit jejunum, trachea, aorta, and guinea-pig atria. RESULTS: Bo.Cr which was tested positive for flavonoids, coumarins, sterols and tannins produced a concentration-dependent relaxation of spontaneous and K+ (80mM)-induced contractions in isolated rabbit jejunum preparations, suggestive of Ca++ antagonist effect, which was confirmed when pretreatment of the tissue with Bo.Cr produced a rightward shift in the Ca++ concentration-response curves like that caused by verapamil. In rabbit tracheal preparations, Bo.Cr relaxed the carbachol (1microM) and K+-induced contractions. Verapamil also produced non-specific inhibitory effect. In rabbit aorta preparations, Bo.Cr exhibited vasodilator effect against phenylephrine and K+-induced contractions similar to verapamil. When tested in guinea-pig atria, Bo.Cr caused inhibition of both atrial force and rate of contractions. CONCLUSIONS: These results suggest that the spasmolytic effects of Bo.Cr are mediated possibly through Ca++ antagonist mechanism, which might explain the traditional use of Borago officinalis in hyperactive gastrointestinal, respiratory and cardiovascular disorders.     

Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice

Oxidative stress is involved in many acute and chronic diseases including cancer, cardiovascular disorders and neurodegenerative diseases. We studied the relationship between the level of intracellular reactive oxygen species in peripheral granulocytes and the estimated anxiety level of mice using the behavioral light/dark choice test. Our results indicate a linear and significant relationship between the intracellular redox status of peripheral blood granulocytes and different parameters of anxiety-related behavior including latency time (R(2)=0.737, P<0.001), cumulative time spent in the lit box (R(2)=0.612, P<0.01) and number of entries into the lit box (R(2)=0.661, P<0.01). These results suggest a positive relationship between peripheral oxidative status and level of anxiety in mice.     

Sacrococcygeal pilonidal disease: sinotomy versus excisional surgery, a retrospective study

Pilonidal disease is a disease of relatively young people, the exact aetiology of which is unknown. Treatment options vary from simple incision to complex flap procedures. Each method has its advocates and they all have a variable recurrence rate. The multiplicity of procedures testifies to the lack of an optimal treatment method. The objective of this study is to compare sinotomy, that is, simply laying the sinus open with the more popular radical surgery, where the sinus-bearing tissues are excised. Patients who were admitted to Aseer Central Hospital, Saudi Arabia with a pilonidal sinus or abscess, in the period from April 1999 to January 2005, were identified. The medical records were reviewed and data related to the patient characteristics, disease process and the procedures carried out were noted. Identified patients were contacted by phone to check recurrence of the disease and their abidance to instructions regarding regular hair removal from the area. Eighty-one patients were included in the study. The median age was 24.2 years (range 16-60 years). There were 9 women and 72 men. All procedures were carried out under general anaesthesia except sinotomy, which was carried out under general or local anaesthesia. The surgical procedure was incision and drainage of abscess in 16 cases (19.8%), excision with primary closure in 29 cases (35.8%), excision by the open method in 15 cases (18.5%), sinotomy in 14 cases (17.3%) and rhomboid flap construction in 8 cases (9.9%). The overall recurrence rate was 26.9%, and the mean hospital stay was 4.1 days. Sinotomy had a low recurrence rate (12.5%) and a short hospital stay (2.8 days). Sinotomy has the advantages of simplicity, the possibility of operating under local anaesthesia, with an acceptable recurrence rate. We recommend sinotomy for pilonidal sinus and abscess alike, both in primary and recurrent cases.     

Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance

Malignant melanoma is one of the most aggressive and invasive metastatic tumors derived from melanocytes that have undergone malignant transformation by acquisition of genetic and epigenetic alterations. Oligonucleotide microarray-based screening of distinct stages in the tumor progression model of cutaneous melanoma identified ASK/Dbf4, as a novel determinant for melanoma development. Quantitative real-time polymerase chain reaction-based confirmation of ASK/Dbf4 on a series of benign nevi, dysplastic nevi, primary cutaneous melanomas and cutaneous melanoma metastases; and a number of other controls using normal human melanocytes as calibrator not only revealed a melanoma-specific over-expression but also revealed that higher ASK/Dbf4-expressing melanomas were associated with lower relapse-free survival. Additionally, we also confirmed the observed over-expression of ASK/Dbf4 in melanoma using western blot analysis and immunohistochemistry. As ASK/Dbf4 is known to be a cyclin-like regulatory subunit of mammalian Cdc7 from the studies in yeast, the present study investigated its role in melanoma cells. In keeping with its expected role, our data suggest that up-regulated ASK/Dbf4 is localized in the nucleus and binds to human Cdc7 to form Cdc7-ASK/Dbf4 complexes in several analyzed melanoma cell lines. Further, we demonstrate that small interfering RNA-mediated depletion of ASK/Dbf4 retarded melanoma cell survival and proliferation. In summary, we report the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggest that up-regulation of ASK/Dbf4 is a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma.     

The feasibility of rib grafts in long span mandibular defects reconstruction: A long term follow up

Aims

To evaluate the efficiency of reconstruction of long span mandibular defects using split rib bundle bone graft.

Combined molecular dynamics simulations and experimental studies of the removal of cationic dyes on the eco-friendly adsorbent of activated carbon decorated montmorillonite Mt@AC

In recent years, the combination of experimental and theoretical study to explain adsorbate/adsorbent interactions has attracted the attention of researchers. In this context, this work aims to study the adsorption of two cationic dyes, namely methylene blue (MB) and crystal violet (CV), on a green adsorbent Montmorillonite@activated carbon (Mt@AC) composite and to explain the adsorption behavior of each dye by the molecular dynamics (MD) simulation method. The eco-friendly nanocomposite Mt@AC is synthesized and characterized by the analysis methods: XRD, FTIR, BET, TGA/DTA, SEM-EDS, EDS-mapping and zeta potential. The experimental results of adsorption equilibrium show that the adsorption of the two dyes is well suited to the Langmuir adsorption model. The maximum adsorption capacity of the two dyes reaches 801.7 mg g⁻¹ for methylene blue and 1110.8 mg g⁻¹ for crystal violet. The experimental kinetics data fit well with a pseudo-first order kinetic model for the two dyes with coefficient of determination R² close to unity, non-linear chi-square χ² close to zero and lower Root Mean Square Error RMSE (R² → 1 and χ² → 0, RMSE lower). Molecular dynamic simulations are run to gain insights on the adsorption process. According to the RDF analysis and interaction energy calculations, the obtained results reveal a better affinity of the CV molecule with both the AC sheet and montmorillonite framework as compared with MB. This finding suggests that CV is adsorbed to a larger extent onto the nanocomposite material which is in good agreement with the adsorption isothermal experiment observations.

Eco-friendly Mt@AC composite material was prepared and characterized for removal of cationic dyes from aqueous solutions. The Molecular dynamics simulation was applied for evaluating the adsorption mechanisms.     

Assessment of serum vascular endothelial growth factor and nail fold capillaroscopy changes in systemic lupus erythematosus with and without cutaneous manifestations

Angiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09-4714.30 vs. 60.00, 14-366, respectively, P?相似文献   

Fluorescence lifetime imaging of activatable target specific molecular probes

In vivo optical imaging using fluorescently labeled self‐quenched monoclonal antibodies, activated through binding and internalization within target cells, results in excellent target‐to‐background ratios. We hypothesized that these molecular probes could be utilized to accurately report on cellular internalization with fluorescence lifetime imaging (FLI). Two imaging probes were synthesized, consisting of the antibody trastuzumab (targeting HER2/neu) conjugated to Alexa Fluor750 in ratios of either 1:8 or 1:1. Fluorescence intensity and lifetime of each conjugate were initially determined at endosomal pHs. Since the 1:8 conjugate is self‐quenched, the fluorescence lifetime of each probe was also determined after exposure to the known dequencher SDS. In vitro imaging experiments were performed using 3T3/HER2⁺ and BALB/3T3 (HER2^?) cell lines. Changes in fluorescence lifetime correlated with temperature‐ and time‐dependent cellular internalization. In vivo imaging studies in mice with dual flank tumors [3T3/HER2⁺ and BALB/3T3 (HER2^?)] detected a minimal difference in FLI. In conclusion, fluorescence lifetime imaging monitors the internalization of target‐specific activatable antibody–fluorophore conjugates in vitro. Challenges remain in adapting this methodology to in vivo imaging. Copyright © 2010 John Wiley & Sons, Ltd.