A potential role of mesenchymal stem cells derived from human umbilical cord blood in ameliorating psoriasis-like skin lesion in the rats.

BACKGROUND: Psoriasis is a common autoimmune inflammatory skin disease, with no clear cause, treated with topical agents and phototherapy, conventional immunosuppressant drugs and biologic agents. Stem cell therapy has generated significant interest in regenerative medicine. The aim of this study was to use mesenchymal stem cell (MSC) therapy compared to the topical application of the standard conventional corticosteroid cream. MATERIALS AND METHODS: Forty male adult albino rats were used, divided into four groups, 10 rats each: group I (control), group II (psoriasis-like lesions induced by usage of Aldara cream), group III (treated with betamethasone) and group IV (treated with MSCs). Specimens were stained with haematoxylin and eosin, Masson's trichrome, immune-histochemical technique for CD4, CD8 and CD31. Ultra-sections were prepared for transmission electron microscope (TEM) examination. RESULTS: Mesenchymal stem cells demonstrated efficacy in reduction of disease severity in the form of uniform epidermal thickness covered by a very thin keratin layer. Normally arranged layers of epidermal layers, with a clear border demarcation, were seen between the epidermis and the dermis with apparently intact basement membrane. TEM showed absence of gaps between the tightly connected cells of the basal layer and the resting basement membrane. CONCLUSIONS: Application of MSCs raises hope for developing a new, safe and effective therapy for psoriatic patients, avoiding the side effects of betamethasone.

Emergence of two novel sublineages Ind2001BD1 and Ind2001BD2 of foot-and-mouth disease virus serotype O in Bangladesh.

Foot-and-mouth disease (FMD) is endemic in Bangladesh, and the implementation of a control programme for this disease is at an early stage, according to the FAO- and OIE-proposed Progressive Control Pathway for FMD (PCP-FMD) Roadmap. To develop an effective control programme, understanding of foot-and-mouth disease virus (FMDV) serotypes, even subtypes within the serotypes is essential. The present investigation aims at viral VP1 coding region sequence-based analysis of FMD samples collected from 34 FMD outbreaks during 2012-2016 in Bangladesh. Foot-and-mouth disease virus (FMDV) serotype O was responsible for 82% of the outbreaks in Bangladesh, showing its dominance over serotype A and Asia1. The VP1 phylogeny revealed the emergence of two novel sublineages of serotype O, named as Ind2001BD1 and Ind2001BD2, within the Ind2001 lineage along with the circulation of Ind2001d sublineage in Bangladesh, which was further supported by the multidimensional scaling with distinct clusters for each sublineage. The novel sublineages had evident genetic variability with other established sublineages within Ind2001 lineage. Ten mutations with three or more amino acid variations were detected within B-C loop, G-H loop and C-terminal region of the VP1 protein of FMDV serotype O viruses isolated exclusively from Bangladesh. Furthermore, two amino acid substitutions at positions 197 and 198 within the VP1 C-terminal region are unique to the novel sublineages. The existence of widespread genetic variations among circulatory FMDV serotype O viruses makes the FMD control programme complex in Bangladesh. Adequate epidemiological data, disease reporting, animal movement control, appropriate vaccination and above all stringent policies of the government are necessary to combat FMD in Bangladesh.

T4 lysozyme fused with cellulose-binding module for antimicrobial cellulosic wound dressing materials.

AIMS: Bacterial infection is a major challenge in wound care. Antimicrobial wound dressings are of great value for treating wound infections. Endolysins are evolving as a new class of antimicrobials with multiple applications. This study describes the production and evaluation of T4 lysozyme (T4Lyz), product of gene e of the T4 bacteriophage, fused with Cellulose Binding Module (CBM) for facile immobilization to cellulosic wound dressing. METHODS AND RESULTS: Genes encoding T4Lyz-CBM and T4Lyz were cloned and expressed in Escherichia coli and the enzymes were purified by cation exchange chromatography. While the CBM tag did not alter the optimum pH and stability features of T4Lyz, the lytic activity of the fusion protein was lowered. The bactericidal activity of T4Lyz-CBM, determined by viable count plating assay after 1 h incubation with Micrococcus lysodeikticus was 97·5% with 10 µg ml(-1) , and 99·96% and 95% for E. coli and Pseudomonas mendocina, respectively, with 200 µg ml(-1) enzyme. T4Lyz-CBM was immobilized to wound dressing gauze with a capacity of 5·5 µg mg(-1) matrix, whereas the unmodified T4Lyz did not exhibit any binding. The immobilized protein retained its bactericidal activity against Gram-positive and Gram-negative bacteria. Both free and immobilized T4Lyz-CBM, after heat denaturation, retained their bactericidal activities against Gram-negative bacteria only. The immobilized enzyme exhibited higher stability than the free enzyme when stored in dry form or in the presence of polyol stabilizers. CONCLUSION: Tagging T4Lyz with CBM provides a facile, irreversible binding to cellulosic wound dressing while retaining its activity. This approach may be suitable even for other antimicrobial enzymes and -peptides. SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of antibiotic resistance requires innovative strategies for discovery and development of effective antimicrobial alternatives. This report presents a novel strategy for producing antimicrobial wound dressing materials.

Molecular characterization of Enterococcus spp. clinical isolates from Cairo, Egypt.

PURPOSE: Enterococci are responsible for serious diseases such as bacteraemia, endocarditis and urinary tract infections. The ability of enterococci to cause such diseases is due to acquisition of certain virulence factors such as haemolysin, gelatinase and enterococcus surface protein. This study has been conducted to investigate the occurrence of virulence factors and resistance to various antibiotics with emphasis on vancomycin in the Enterococcus spp. MATERIALS AND METHODS: Clinical specimens were collected and isolates were identified by proper microscopic, culture and biochemical tests. Susceptibility and degree of resistance of the isolates to various antibiotics were determined. Virulence factors were examined by phenotypic tests followed by molecular methods. Bioinformatics analysis was used to detect regions in the genomes that might have originated from horizontal gene transfer. RESULT: The presence or absence of virulence genes did not affect the pattern of antimicrobial resistance in Enterococcus isolates; consequently, no relationship was found between virulence factors and resistance to different antibiotics used. Bioinformatics analysis showed that the virulence genes were mainly transferred by transposons. CONCLUSION: Among the enterococci, environmental factors may interfere in the expression of virulence factors. Horizontal gene transfer plays an important role in the spread of resistance and virulence genes.

Precipitating factor of seizure in epilepsy: experience in a tertiary care hospital.

Patients with epilepsy experience recurrent, unprovoked seizures. In most of the cases seizure occurs spontaneously, but there may be association with various triggers. These triggers may act as seizure precipitating factors (SPFs). This study was done to find out the most common SPFs and their relationship to different types epileptic patients attending a tertiary care hospital in Bangladesh. This cross sectional study was carried out in specialized epilepsy weekly outdoor clinic and Medicine outpatient department (OPD) of Dhaka Medical College Hospital from January 2008 to July 2011, which included 1168 epilepsy patients. All patients attending the clinic were included in the study. Epilepsy syndromes were broadly classified into four categories using the classification system of international league against epilepsy (ILAE) namely, generalized epilepsy (GE), localization related epilepsy (LRE), symptomatic and unclassified. Each patient was evaluated and classified by consultant neurologist. All participants were interviewed through a predesigned close ended questionnaire that included a long list of 30 precipitating factors. Among all the patients 71.5% were male, with most common age group 11-20 years (36.8%). About 62% could indentify at least one precipitator. Excitation (25.2%) was the most common SPF reported by patients followed by emotional stress in 17.7%. Fever precipitated seizure in 16.4% of the subjects. A good number of them (15.5%) noticed that whenever there was sleep deprivation, they had an attack of epilepsy. However, drug withdrawal, playing outside and head trauma were also common among the patients, about 11.7%, 11.3% and 8.4% respectively. Most of the patients can identify their seizure precipitant and clustering of many SPFs suggests a common patho-physiologic mechanism for these triggers. Excitation, sleep deprivation, fever, watching television and head trauma showed a strong association with generalized epilepsy. Patients with seizure disorder should be evaluated for presence of SPFs, because identification of these might help in proper management of epilepsy.

Site selectivity in reactions of hydrazonoyl halides with heterocycles containing amino and thione groups leading to fused heterocycles of potential antimicrobial activity.

Reaction of hydrazonoyl halides with 6-(benzylidenamino)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one and 2,3-diaminoquinazolin-4-one site-selectively afforded 3-substituted-7-(benzylidenamino)-1-phenyl-[1,2,4]triazolo[4,3-a]-pyrimidin-5(1H)-ones, [1,2,4,5]tetrazino[6,1-b]quinazolin-6(4H)-one, and 3-methyl-2-(4-substituted-phenylhydrazo)-[1,2,4]triazino[3,2-b]quinazolin-10-ones in good yields. The structures of the newly synthesized compounds were elucidated by chemical evidence and their IR, 1H, 13C NMR, and MS spectra. Furthermore, some of the products were screened against different strains of bacteria and fungi.

Anti-thymocyte globulins capable of binding to T and B cells reduce graft-vs-host disease without increasing relapse.

Anti-thymocyte globulin (ATG) is polyclonal, containing Ab specificities capable of binding to various immune-cell subsets implicated in the pathogenesis of GVHD, including T cells, B cells, natural killer cells, monocytes/macrophages, neutrophils and DC. We wished to determine which ATG specificities are important for GVHD prevention. We measured day 7 serum levels of 23 ATG specificities in 120 hematopoietic cell transplant recipients whose myeloablative conditioning included 4.5 mg/kg ATG (thymoglobulin). High levels of ATG specificities capable of binding to T- and B-cell subsets were associated with a low likelihood of acute GVHD (aGVHD). High levels of these ATG specificities were associated with increased rates of viral but not bacterial or fungal infections. They were not associated with an increased risk of malignancy relapse; on the contrary, high levels of ATG specificities capable of binding to regulatory T cells and invariant NKT cells were associated with a low risk of relapse. In conclusion, high levels of ATG antibodies to Ag(s) expressed on T and B cells are associated with a low risk of aGVHD and a high risk of viral but not bacterial or fungal infections. These antibodies have neutral or beneficial effects on relapse.

Iatrogenic tracheal flap mimicking tracheal stenosis with resultant stridor.

OBJECTIVE: To illustrate a case of an iatrogenic mucosal tear in the trachea which caused a one-way valve effect, obstructing the airway and manifesting as post-extubation stridor. CASE REPORT: We report a case of iatrogenic tracheal mucosal tear secondary to violent movement during intubation. The patient presented with post-extubation stridor that worsened over three days. Initial evidence suggested tracheal stenosis. Computed tomography scans revealed a mucosal tear at the level of the seventh cervical to second thoracic vertebrae. The tear was caused by forceful inflow of air as breathing became more and more difficult, resulting in a false tract. A tracheostomy changed the direction of airflow, bypassing the tear. The inflated tracheostomy tube cuff acted as a stent to keep the flap in place as healing occurred. CONCLUSION: Iatrogenic laryngotracheal injuries are common, especially when endotracheal intubation is performed under unfavourable emergency conditions. A tracheal mucosal tear is a rare entity which is almost always undiagnosed. However, a tracheal mucosal flap may be suspected when changes in patient position alter the nature and severity of the resultant stridor and/or respiratory distress. In such cases, an inflated tracheostomy tube cuff should be kept in place for an adequate period, to act as a stent and help keep the flap in place while healing occurs.

Biological treatment of industrial wastes in a photobioreactor.

An algal-bacterial consortium was tested for the treatment from a coke factory. A Chlorella vulgaris strain and a phenol-degrading Alcaligenes sp. were first isolated from the wastewater treatment plant to serve as inocula in the subsequent biodegradation tests. Batch tests were then conducted with samples from the real wastewater or using a synthetic wastewater containing 325 mg phenol/l and 500 mg NH4+/l as target pollutants. Direct biological treatment of the real wastewater was not possible due to the toxicity of organic compounds. Activated carbon adsorption and UV(A-B)-irradiation were efficient in detoxifying the effluent for subsequent biological treatment as inoculation of pretreated samples with the algal-bacterial consortium was followed by complete phenol removal and NH4+ removal of 45%. Complete phenol removal and 33% NH4+ removal were achieved during the fed-batch treatment of artificial wastewater at 6 d hydraulic retention time (HRT). Under continuous feeding at 3.6 d HRT, phenol and NH4+ removal dropped to 58 and 18%, respectively. However, complete phenol removal and 29% NH4+ removal were achieved when 8 g NaHCO3/l was added to the artificial wastewater to enhance algal growth. This study confirms the potential of solar-based industrial wastewater treatment based on solar-based UV pretreatment followed by algal-bacterial biodegradation.

Progress achieved in the elimination of schistosomiasis from the Jazan region of Saudi Arabia.

Among the inhabitants of the Jazan region of Saudi Arabia, the prevalence and intensity of Schistosoma haematobium infection have been kept very low for several years, by sustained control efforts. The success of the interventions, which were based on case finding, the treatment of infected individuals, and the chemical and environmental control of freshwater snails, led, in mid-2002, to a strategy to eliminate human infection with S. haematobium from Jazan. The strategy, which was based on regular chemotherapy, snail control (made easier by the focality of transmission in the area) and health education, with screening at primary-healthcare centres, by mobile teams and at diagnostic units, appears to have been successful. No infected snails can now be found in the region and new cases of human infection with S. haematobium are only being detected in border villages (and are attributed to infections beyond the region, in areas where active transmission is still taking place). Total elimination appears possible if the health authorities in neighbouring areas can be persuaded to adopt a similar strategy of control.

Use of the buccal fat pad in the reconstruction and prosthetic rehabilitation of oncological maxillary defects.

We evaluated the effectiveness of the buccal fat pad as a pedicled flap for intraoral reconstruction after partial maxillectomy for neoplastic disease in 24 patients, and subsequently, in providing support for a denture. In all patients the buccal fat pad was covered with a split-skin graft and an acrylic plate. There was complete healing of the buccal fat pad flap within 6 weeks in 18 patients with no major complications, and minimal effects on speech and eating. In six cases there was partial dehiscence of the flap, which healed spontaneously in one patient and was repaired with local flaps in two others. There were no cases of complete breakdown of the flap. Eight patients so far have been rehabilitated with small dentures. In conclusion, the buccal fat pad flap is a simple, quick, and reliable method of reconstruction of small to medium-sized posterior maxillary alveolar defects.

Effects of bisphenol-A on the growth of comb and testes of male chicken.

Bisphenol-A (BPA) has been reported to have some xenoestrogenic effects on the reproductive system of male animals. In this study, we examined the growth of combs and testes of the male chickens exposed to BPA. White leghorn male chicks were administered 200 mg BPA orally every week from 2 wk of age. The combs and testes were examined at 16 wk of age. The body growth showed no significant difference between BPA-administered and control birds. However, the weight of the combs and testes were lower in the BPA-treated birds. Histologically, testes of the control birds were well matured; the seminiferous tubuli were filled with sperm. In contrast, the testes of most of the BPA-treated birds showed an immature appearance with smaller seminiferous tubuli and limited spermatogenesis. These findings suggest that the xenoestrogenic property of BPA might disturb the growth of the comb and testes of male chickens by a possible endocrine disrupting mechanism.

Delay in the diagnosis and prognosis of caecal carcinoma--a study of 20 cases.

BACKGROUND: Caecum is the dilated part of the right colon situated in the right iliac fossa, therefore the etiology of this cancer is similar to those of the rest of the colon. Caecal carcinoma is more common in developed countries but it is not a rare disease in underdeveloped countries. This is more common in high socio-economic people who use less fibrous and purified diet. With improvement in health education and social status of the people of Pakistan, there is an emerging trend of Westernization in our society. This may increase the incidence of cancer in Pakistan. Carcinoma of caecum is curable disease is diagnosed early and treated. If we are aware of the pathogenesis, etiology, clinical presentation and management of the disease, we can offer a lot to these patients by diagnosing the caecal carcinoma at an earlier stage, this was the aim of this study. METHODS: 20 cases (15 males and 5 females) of Carcinoma of Caecum were studied from January 1997 to December 1999. Out of these six patients presented in emergency ward, 2 as acute appendicitis and 4 as intestinal obstruction. After routine non-specific investigations, our specific investigations included USG abdomen, barium contrast studies and colonoscopy, Barium study and USG remained of primary importance. RESULTS: Most of the patients were between age 45-65 years, oldest patient being 80 years old and the youngest was of only 30 years. Most of the patients presented as mass in the right iliac fossa and only some patients as intestinal obstruction. Right hemicolectomy with primary ileo-transverse anastomosis was our standard surgical procedure and was done in about 14 cases. But in some cases ileo-transverse by-pass operation was done as the growth was locally advanced. However, only the omental biopsy was taken in the cases where carcinoma was too advanced. CONCLUSIONS: We think that our sociodemographic factors put a hindrance in detection of this carcinoma at early stages and therefore curative procedures are difficult to bear good results.

Congenital atresia of the orifice of the submandibular duct: a report of 2 cases and review.

Two infants presented with unilateral cystic swellings in the floor of the mouth as a result of imperforate submandibular ducts. This is thought to result from a congenital failure of canalization of the terminal end of the duct. Both cases responded to simple incision and decompression of the fluid-filled duct. Early treatment is important to avoid feeding difficulties and to prevent later complications such as ranula or sialadenitis.

Clinical and radiological evidence to support superficial parotidectomy as the treatment of choice for chronic parotid sialadenitis: a retrospective study.

We present a retrospective series of 23 consecutive parotidectomies, over a 10-year period (1989-1999) for 22 patients with chronic sialadenitis unresponsive to conservative measures. There were 10 male and 12 female patients. Mean age was 52 years (range 12-72), and mean duration of symptoms 4.5 years (range 8 months-30 years). All patients had preoperative sialography and 2 had computed tomography to exclude a neoplasm. A complete superficial parotidectomy with preservation of the main duct was done in all cases. Fifteen patients developed temporary facial nerve weakness postoperatively and 7 developed Frey's syndrome. There were no cases of permanent facial nerve palsy. Nineteen patients reported complete resolution of their symptoms and 3 patients had mild persisting symptoms that did not necessitate any further treatment. Histologically there was evidence of sialadenosis in one case and benign lymphoepithelial lesion in another; the others showed evidence of chronic sialadenitis of varying degrees of severity. Fifteen patients had postoperative sialograms, of which 11 showed evidence of some filling of residual parotid gland parenchyma and in 8 patients there was filling of a normal-looking accessory lobe. In this series, superficial parotidectomy with preservation of the main duct was safe and effective, with minimal long-term complications, for most patients with chronic parotid sialadenitis that was unresponsive to conservative measures and, in some patients, it allowed some preservation of function. The potential damage to the facial nerve and the cosmetic problems associated with a total or near-total parotidectomy were avoided.

Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis.

Angiogenesis is an important aspect of the vasculoproliferation found in the rheumatoid arthritic (RA) pannus. We have previously implicated members of the CXC chemokine family as potent angiogenic mediators in RA. We investigated the possibility that the sole member of the CX(3)C chemokine family, fractalkine (fkn), induces angiogenesis and that fkn might mediate angiogenesis in RA. Recombinant human fkn significantly induced migration of human dermal microvascular endothelial cells (HMVECs), a facet of the angiogenic response, in the pmol/L range in a concentration-dependent manner (P < 0.05). Fkn also induced the formation of significantly more endothelial tubes on Matrigel than did a negative control (P < 0.05). Fkn significantly induced 2.3-fold more blood vessel growth than control in the in vivo Matrigel plug assays (P < 0.05). We identified HMVEC expression of the fkn receptor, CX(3)CR1. Next, we determined if RA synovial fluid (SF)-induced angiogenesis was fkn-dependent. SFs from six RA patients immunodepleted of soluble fkn induced 56% less migration of HMVECs than did sham-depleted RA SFs (P < 0.05). In vivo, immunodepletion of fkn from six RA SFs significantly inhibited their angiogenic activity in Matrigel plug assays (P < 0.05). Immunodepletion of fkn from five RA synovial tissue homogenates inhibited their ability to induce angiogenesis in in vivo Matrigel plug assays (P < 0.05). These results establish a new function for fkn as an angiogenic mediator and suggest that it may mediate angiogenesis in RA.

Evidence of IL-18 as a novel angiogenic mediator.

Angiogenesis, or new blood vessel growth, is a key process in the development of synovial inflammation in rheumatoid arthritis (RA). Integral to this pathologic proliferation are proinflammatory cytokines. We hypothesized a role for IL-18 as an angiogenic mediator in RA. We examined the effect of human IL-18 on human microvascular endothelial cell (HMVEC) migration. IL-18 induced HMVEC migration at 1 nM (p < 0.05). RA synovial fluids potently induced endothelial cell migration, but IL-18 immunodepletion resulted in a 68 +/- 5% decrease in HMVEC migration (p < 0.05). IL-18 appears to act on HMVECs via alpha(v)beta(3) integrin. To test whether IL-18 induced endothelial cell tube formation in vitro, we quantitated the degree of tube formation on Matrigel matrix. IL-18, 1 or 10 nM, resulted in a 77% or 87% increase in tube formation compared with control (p < 0.05). To determine whether IL-18 may be angiogenic in vivo, we implanted IL-18 in Matrigel plugs in mice, and IL-18 at 1 and 10 nM induced angiogenesis (p < 0.05). The angiogenesis observed appears to be independent of the contribution of local TNF-alpha, as evidenced by adding neutralizing anti-TNF-alpha Ab to the Matrigel plugs. In an alternative in vivo model, sponges embedded with IL-18 or control were implanted into mice. IL-18 (10 nM) induced a 4-fold increase in angiogenesis vs the control (p < 0.05). These findings support a novel function for IL-18 as an angiogenic factor in RA and may elucidate a potential therapeutic target for angiogenesis-directed diseases.

IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis.

IL-4 is a cytokine with anti-inflammatory properties on activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory disease, is characterized by a paucity of IL-4 and an abundance of synovial macrophage-derived mediators. Herein, the effect of a single injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared with the effect of PBS injection into rat ankles. Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduced adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle inflammation, decreasing articular index scores, ankle circumferences, paw volumes, radiographic scores, mean levels of monocyte chemoattractant protein-1, the number of inflammatory cells, and the number of synovial blood vessels. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS groups. After arthritis onset, mean levels of TNF-alpha, IL-1beta, macrophage inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates compared with PBS-treated homogenates. Thus, increased expression of IL-4 via gene therapy administered in a preventative and/or therapeutic manner reduced joint inflammation, synovial cellularity, levels of proinflammatory cytokines, vascularization, and bony destruction in rat AIA, suggesting that a similar treatment in humans may be beneficial.

Diagnosis of deep vein thrombosis in the leg by using colour coded duplex sonography.

BACKGROUND: Deep Vein Thrombosis (DVT) is regarded rare [not readable: see text] Asia. There is no documentation of the incidence of DVT in Pakistan. Clinical diagnosis of Deep Vein Thrombosis is inaccurate. Venography is the most reliable method of diagnosis, but it has several disadvantages. Many non-invasive diagnostic methods have therefore been developed in the past decade. Of these only duplex sonography has comparable accuracy. METHODS: We studied 100 cases of suspected DVT by using colour coded duplex sonography. We report the results of a prospective study in patients with suspected deep vein thrombosis evaluated by both colour coded Doppler sonography and venography. CONCLUSION: We conclude that colour coded duplex sonography is a highly accurate, simple, non-invasive method for detecting femoropopliteal thrombosis. Additional venography is not necessary. Its value in diagnosing isolated calf vein thrombosis remains to be established.

Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by leukocyte recruitment and angiogenesis. We investigated the effects of sulfasalazine (SSZ) and its metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA), on components of angiogenesis, namely, endothelial cell (EC) chemotaxis and proliferation, as well as on EC chemokine and soluble adhesion molecule expression. METHODS: SSZ, SP, and 5-ASA were assayed for their effects on basic fibroblast growth factor (bFGF)-induced human dermal microvascular endothelial cell (HMVEC) chemotaxis and proliferation. EC were plated on Matrigel to assess the effect of SSZ on EC tube formation. Enzyme-linked immunosorbent assays were performed to determine changes in HMVEC production of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), growth-related oncogene alpha (GROalpha), epithelial neutrophil-activating peptide 78 (ENA-78), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule 1 (sICAM-1) upon treatment with SSZ or its metabolites. RESULTS: HMVEC incubated with SSZ or SP exhibited reduced bFGF-induced chemotaxis (59%, [n = 7] and 22%, [n = 3], respectively) (P<0.05). SSZ and SP decreased basal HMVEC proliferation, while 5-ASA increased proliferation (P<0.05; [n = 5]). SSZ decreased bFGF-induced HMVEC proliferation (P<0.05 [n = 5]). SSZ inhibited phorbol 12-myristate 13-acetate-induced HMVEC tube formation (P<0.05; [minimum n = 5]). Tumor necrosis factor alpha-stimulated HMVEC shedding of sICAM-1 was reduced by incubation with either SSZ (19%) or 5-ASA (23%) (P<0.05; [n = 6]). SP inhibited cytokine-stimulated HMVEC expression of IL-8 and MCP-1 (P<0.05; [n = 4]). Neither SSZ nor its metabolites had any effect on HMVEC production of sE-selectin, GROalpha, or ENA-78. CONCLUSION: These results demonstrate that SSZ and its metabolite SP may affect the pathogenesis of RA by inhibiting EC chemotaxis, proliferation, tube formation, and expression of sICAM-1, IL-8, and MCP-1.