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Biomedical subjects

M A Amin

Publications and source records attributed to M A Amin.

At least 19 recordsLinked to original sources

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.

Angiogenesis Inducing Agents↗

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.

Adenoviruses, Human↗

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.

Arthritis, Rheumatoid↗

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.

Adolescent↗

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.

Humans↗

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.

Anti-Infective Agents↗

Integration of schistosomiasis-control activities into the primary-health-care system in the Gizan region, Saudi Arabia.

A few decades ago, the prevalence of Schistosoma haematobium infection in the human inhabitants of the Gizan region of Saudi Arabia was very high (43%-91%). A vertical programme for the control of the disease, by case finding, treatment of infected individuals and by chemical snail control, was begun in 1974 and led to significant reductions in prevalence in most areas. In 1989 the control activities were gradually integrated into the primary-health-care (PHC) system. Several schools in the area recently participated in the detection of ova (among schoolchildren and neighbouring communities) and organized health-education sessions. The records taken during the vertical and PHC programmes indicate that there were more diagnoses and higher chemotherapy coverage in the latter. The PHC programme has maintained the overall prevalence of infection at an extremely low level (< 1%) and the infection has been completely eradicated in several areas. The participation of schools proved to be particularly useful in terms of population coverage and health education.

Animals↗

Serum LDH and ALP isozyme activities in mice bearing solid Ehrlich carcinoma and/or treated with the maximum tolerated dose (MTD) of aloin.

Determination of total LDH and ALP activities and their isozyme patterns in the sera of normal and tumour-bearing animals treated with aloin, a natural anthraquinone with potential antitumour activity, was carried out at 3, 6 and 9 weeks of treatment. Treatment of normal mice with the MTD of aloin (50 mg/Kg b.w.) showed non-significant changes in serum total LDH and ALP activities along with their isozymes throughout the experimental periods. In untreated tumour-bearing animals, serum LDH activity and its isozymes: LDH1-LDH5 showed highly significant increases (192, 32.4, 25.2, 24.7, 29.2 and 30.6%, respectively) after 3 weeks. Highly significant inhibition was recorded in serum total ALP activity and its intestinal and bone isozymes (64, 100 and 56%, respectively), while liver ALP isozyme was increased by 82.3%. Treatment of tumour-bearing mice with the MTD of aloin manifested a significant gradual improvement in both enzyme activities and their isozymes, which were normalized at the end of the experiment (9 weeks), with the exception of intestinal ALP isozyme. All results were reported in comparison to the normal control group.

Alkaline Phosphatase↗

Falls in the elderly.

Finally, we conclude with a reminder that the causes of falls in the elderly are multifactorial and that some of these factors may be summative. Most falls result from interaction of intrinsic and extrinsic (environmental) factors. In the Emergency Department, it is very important to take a detailed history of the circumstances leading to the fall and to perform a thorough physical examination. Every attempt should be made to identify predisposing factors for the fall and for preventive measures to be initiated. These may include geriatric consultation or a home visit to evaluate home environment. There is a great need for additional research in this field. Falls are one of the syndromes common in the elderly that deserve more careful attention and are considered amenable to both primary and secondary prevention measures.

Accidental Falls↗

The lungfish Protopterus annectans (Owen) as a biocontrol agent against schistosome vector snails.

Laboratory and small-scale field experiments have been carried out to study the malacophagous capabilities of the lungfish Protopterus annectans. When individual fish were offered a range of aquatic fauna in aquaria in the laboratory only snails and dragonfly larvae were consumed. When offered a choice, the fish appeared to prefer snails, with larger individuals (up to 300 mm) capable of consuming up to 200 snails per day. The introduction of five P. annectans into a small concrete pond (diameter 5 m) with an established fauna and flora resulted in a reduction in the snail population of over 90% within 2 weeks. This reduction was maintained over a 4-month observation period suggesting that in habitats in which the lungfish can survive, there is a possibility of significant snail control.

Animals↗

Focality and seasonality of Schistosoma mansoni transmission in the Gezira Irrigated Area, Sudan.

In the Gezira Irrigated Area of Central Sudan, transmission of Schistosoma mansoni was shown to be geographically focal, being concentrated near villages and small settlements. In a study during 1981 and 1982 of the entire area around a typical Gezira village almost 90% of the Biomphalaria pfeifferi snails carrying schistosome infections were found in one minor canal near the village. Sites near smaller settlements some distance from the minor canals yielded few infected snails. The factors which influenced the prevalence of infection in the snails were temperature, turbidity and human contact with the snail habitat. A strategy was proposed for control of Schistosoma transmission through focal and seasonal mollusciciding, health education, chemotherapy, improved water supply and latrine distribution.

Agriculture↗

Domestic and wild animals naturally infected with Schistosoma mansoni in the Gezira Irrigated Scheme, Sudan.

Domestic and wild animals were examined for natural infection with human schistosomiasis in Northern Gezira, Sudan. Postmortem examination of animals in a number of slaughterhouses revealed no infections in either sheep or goats but Schistosoma mansoni worms were found in two of the 98 cattle examined. Nile rats (Arvicanthus niloticus) were trapped and stray dogs were shot and examined for evidence of schistosome infection. The infection rate in Nile rats was 4.9% (8/164) and in dogs 27.3% (15/55) but whereas viable eggs were found in the excreta and tissues of the rats no eggs could be found in dog faeces. In the laboratory nine puppies were each exposed to 10 000 cercariae but there was no evidence that the infection had taken. It is concluded that A. niloticus, present in large numbers and often found in or near the canals, may be involved in S. mansoni transmission and could act as reservoir hosts, but that dogs are probably infected only in exceptional situations and are unlikely to play a major role in S. mansoni transmission.

Abattoirs↗

A field trial using praziquantel (BiltricideR) to treat Schistosoma mansoni and Schistosoma haematobium infection in Gezira, Sudan.

A field trial was conducted in the Gezira, Sudan, to evaluate the acceptability and efficacy of praziquantel, a new schistosomicide. In one Arab village 350 patients with Schistosoma mansoni were randomly assigned to two treatment groups and given 1 X 40 mg kg-1 (Group A) or 2 X 20 mg kg-1 given four to six hours apart (Group B). In two small settlements (camps) 2 km distant from the Arab village 38 patients with S. mansoni and 43 with concurrent S. mansoni and S. haematobium infections were given 1 X 40 mg kg-1. Side effects were mild and limited to the first 24 hours after treatment. The main complaints were abdominal pain, diarrhoea, urticaria and/or vomiting and were most common in the camp residents (79%) with 60% of Group A and 45% of Group B having one or more side effects. One month after treatment 'cure' rates were: Camps 63%, Group A 84% and Group B 96%, and the reduction in egg output was over 95%. After 12 months re-infection was greater in the camps. As there was no significant difference in the egg output reduction between the two treatment regimes, praziquantel is recommended for mass chemotherapy in Gezira at the logistically simpler regimen of 1 X 40 mg kg-1.

Adolescent↗

Marking snails with nail varnish as a field experimental technique.

The use of nail varnish to mark snails for release and recapture in aquatic habitats in the Gezira Irrigation Canals has been evaluated. The nail varnish withstood immersion in canal water and adhered to the snail shell. The recovery of marked snails from a backwater site in a slow moving canal was satisfactory and indicated the usefulness of the technique in predicting changing patterns of immigration and emigration of snails. The method may also indicate ecological changes which affect the stability and mobility of snail populations and yield data on growth rates and longevity.

Animal Identification Systems↗