Anti-inflammatory effect of a novel locally acting A2A receptor agonist in a rat model of oxazolone-induced colitis.

Adenosine represents a powerful modulating factor, which has been shown to orchestrate the scope, duration, and remission of the inflammatory response through the activation of four specific receptors, classified as A1, A2A, A2B, and A3, all being widely expressed in a variety of immune cells. Several selective A2A receptor agonists have displayed anti-inflammatory effects, through the suppression of IL-12, TNF, and IFN-γ production by monocytes and lymphocytes, in the setting of chronic intestinal inflammation. However, the therapeutic application of A2A receptor agonists remains hindered by the risk of serious cardiovascular adverse effects arising from the wide systemic distribution of A2A receptors. The present study focused on evaluating the anti-inflammatory effects of the novel poorly absorbed A2A receptor agonist PSB-0777 in a rat model of oxazolone-induced colitis as well as to evaluate its cardiovascular adverse effects, paying particular attention to the onset of hypotension, one of the main adverse effects associated with the systemic pharmacological activation of A2A receptors. Colitis was associated with decreased body weight, an enhanced microscopic damage score and increased levels of colonic myeloperoxidase (MPO). PSB-0777, but not dexamethasone, improved body weight. PSB-0777 and dexamethasone ameliorated microscopic indexes of inflammation and reduced MPO levels. The beneficial effects of PSB-0777 on inflammatory parameters were prevented by the pharmacological blockade of A2A receptors. No adverse cardiovascular events were observed upon PSB-0777 administration. The novel A2A receptor agonist PSB-0777 could represent the base for the development of innovative pharmacological entities able to act in an event-specific and site-specific manner.

An Initiative Technique to Facilitate Axillary Vein Puncture During CRT Implantation.

OBJECTIVES: The aim of the study was to describe a new technique to minimize requirement of contrast and the time to puncture the axillary vein during implantation of cardiac resynchronization therapy (CRT) devices. BACKGROUND: One of the challenges to the wide applications of CRT has been the technical difficulty encountered while obtaining venous access utilizing axillary venous puncture. This is mainly due to vague anatomical land marks. The axillary vein is the preferred access point because of fewer associated risks and better lead protection in the future. METHODS: We introduced a 0.035 mm guidewire retrogradely from the femoral vein up to the left axillary vein. A single anteroposterior scene at 7.5 frames/second was captured while the guidewire was in the vein. The scene was kept as a roadmap for the axillary vein puncture during the implantation procedure. RESULTS: The axillary vein was accessed in all patients (100%) and the time to axillary vein puncture was <1 minute in 36 patients (41%) and between 1-5 minutes in the remaining patients. There were no related vascular complications and no contrast venography was required. CONCLUSION: The use of retrograde axillary vein wiring simplifies axillary venous puncture and minimizes the need for contrast media during CRT device implantation without compromising visualized anatomy.

Polyoma virus nephropathy, first reported case in Saudi Arabia.

Polyoma virus nephropathy (BK virus) is being recognized as an important cause of graft failure. It is usually confused with acute rejection. No cases have been reported from the kingdom of Saudi Arabia. We report a case of a Saudi gentleman, who was transplanted outside the country, with persistently elevated creatinine and urethral stenosis. He was treated for acute rejection on more than one occasion with no significant improvement in his renal function. Polyoma virus nephropathy was diagnosed by detecting the virus DNA by the Poly chain reaction technique (PCR). The patient's renal function stabilized after the calcineurin inhibitors were discontinued.

The interaction between Newcastle disease virus and Escherichia coli endotoxin in chickens.

The interaction between Newcastle disease virus (NDV) and Escherichia coli endotoxin was studied in cell cultures, embryonated chicken eggs, and 8-wk-old chickens. These interactions were evaluated according to the induction of specific or nonspecific resistance in the host system and the virus titer produced in both chicken embryos and chickens. The endotoxin of E. coli induced a decrease in the size of the bursa of Fabricius in live chickens. Escherichia coli endotoxin given intravenously induced plasma antiviral activity in chickens that was interpreted to be interferon, as detected in a vesicular stomatitis virus plaque reduction assay. Endotoxin failed to produced toxic effects in the chicken embryo fibroblasts (CEFs) or to result in any antiviral effect because no change was noted in the number of NDV plaques formed in CEF cultures. When endotoxin was given 3 days before NDV exposure in chickens, the virus titers were significantly (P < 0.05) decreased from a peak of 10(2) to 10(0.18), 10(2.5) to 10(0.18), and 10(2.5) to 0 in the spleens, lungs, and kidneys, respectively, at 72 hr post-NDV inoculation. When endotoxin was given 24 hr after NDV inoculation, the NDV titer significantly (P < 0.05) increased from 10(2.0) to 10(3.5), 10(2.5) to 10(6.5), 10(2.5) to 10(4.5), 0 to 10(2.5) in the spleen, lungs, kidneys, and liver, respectively, at 72 hr after NDV inoculation. In chicken sera, hemagglutination inhibition (HI) titer to NDV was significantly (P < 0.05) enhanced from 1164 to 3127 when endotoxin was given prior to virus inoculation. However, there was a decrease in HI to NDV from 1164 to 727 without a significant difference in chicken sera when NDV was given prior to endotoxin inoculation.

The prevalence of antibodies to hepatitis C virus in Hail region, Saudi Arabia.

The prevalence of subjects positive for anti-HCV antibodies was studied at Hail region Kingdom of Saudi Arabia (KSA). The study involved 8862 subjects tested for anti-HCV antibodies at King Khalid General Hospital during the years 1994-Using Elisa, a total prevalence of 5.09% positive subjects was found. The disease is shown to be mainly acquired at school age and adulthood. Unlike hepatitis B virus, vertical transmission among preschool children does not seem to have an important role in transmission of HCV virus. Egyptians had a high prevalence of 26% as compared to other expatriates. Blood donors had a prevalence of 4.3% which is higher than that reported from other regions in Saudi Arabia. Medical staff had a prevalence rate of 2.2% indicating a relatively low risk of infection. Dialysis patients had a prevalence of 6.9% which is lower than that reported from other regions in Saudi Arabia. The higher prevalence of HCV infection in Hail (which has a lower socioeconomic status) compared to those in Riyadh and Eastern province suggests the possibility of other modes of transmission.

PATTERN OF HBsAg POSITIVITY IN SELECTED GROUPS AT KING KHALID GENERAL HOSPITAL - HAIL REGION, KINGDOM OF SAUDI ARABIA.

BACKGROUND: Hepatitis B virus (HBV) is endemic in the Kingdom of Saudi Arabia. The acquisition of infection occurs early in life. The availability of safe and efficacious vaccines has led to the feasibility of an effective control of HBV infection. This study compares the pattern of HBsAg positivity among selected groups of patients with similar groups in other regions in the Kingdom of Saudi Arabia. OBJECTIVES: This study is conducted to determine the prevalence of HBsAg positive subjects among selected groups of patients attending the main general hospital in the Hail region. SUBJECTS AND METHODS: This retrospective study included 14029 subjects that were tested for HBsAg at King Khalid General Hospital, during the period from April 1994 to April 1996. RESULTS AND DISCUSSION: The overall prevalence of HBsAg positive subjects was 3.5%. The prevalence for Saudis was about 3.2% for Saudis. Pakistanis had the highest prevalence of 11.8%. The prevalence was 3.02% for blood donors, and 2.1 % among pregnant women. No significant difference was found among different age groups. Hail region had a lower prevalence of HBsAg positive cases compared to that estimated by previous studies in the Kingdom, suggesting success in efforts applied by the Ministry of Health (110H) for prevention of Hepatitis B viral infection. CONCLUSION: We can conclude that the prevalence of HBsAg positive subjects is declining in the Hail region, Kingdom of Saudi Arabia (KSA). This decline suggests the success of preventive efforts such as vaccination of newborns with the HBsAg vaccine. However, screening of pregnant women for HBsAg scents to be necessary.

Wilson's disease in Saudi Arabia: Report of a Saudi Arab family.

A Saudi family with Wilson's disease (hepatolenticular degeneration) is described. The index case presented with anicteric hepatitis and hydrops of the gallbladder. Neurological involvement appeared later. The diagnosis of Wilson's disease was based on the presence of Kayser-Fleischer rings, a low serum ceruloplasmin level, and an elevated urinary copper concentration. Histological examination of the liver biopsy specimen revealed active cirrhosis. Acute hepatic failure developed during D-penicillamine therapy. Continuation of the drug at a lower dose, along with other supporitve measures, was successful in reversing this. After three years of therapy, the index patient's neurological signs disappeared, and liver function and gallbladder size and function returned to normal. Family screening revealed that three other siblings have the disease, and all have been treated with D-penicillamine. The parents are related but are asymptomatic. An unusual feature of the index case was the presence of a distended nonfunctioning gallbladder that reverted to normal with decoppering. Although D-penicillamine treatment possibly precipitated the acute hepatic failure, paradoxically it was also successful in treating it.

The 'hybrid' fibro-osseous lesion.

A hitherto unreported 'hybrid' fibro-osseous lesion involving the nasal cavity and sinuses is reported. This lesion histologically demonstrated features of ossifying fibroma, cementifying fibroma and aneurysmal cyst. Whilst appearing benign in nature it behaved in a neoplastic manner which necessitated complete surgical excision. A combined clinical, radiological and histopathological approach is advocated and discussed in relation to the treatment of these lesions.

Influence of limestone level in high concentrate and high roughage diets on site and extent of digestion in lambs.

Two digestion and slaughter trials were conducted to evaluate the influence of limestone level on site and extent of digestion and rumen fermentation in lambs. In trial 1, 11 wether lambs (avg wt 40.7 kg) were fed 75% concentrate diets supplemented with .6, 1.5 or 3.0% limestone (.6,1.2,1.7% dietary Ca, respectively) in a completely randomized design. Dry matter intake increased linearly (P less than .10) with limestone level; therefore, other data were analyzed with dry matter intake as a covariate. Total tract organic matter digestion decreased linearly (P less than .05) with increasing limestone but dry matter and fiber digestion were not affected by limestone. Ruminal digestion of dry matter and organic matter declined linearly (P less than .05) with increasing limestone. Ruminal neutral detergent fiber (NDF) digestion was higher with the 1.5 than the .6 and 3.0% limestone diets (quadratic effect, P less than .05) but ruminal digestion of other fiber components was not affected by limestone. Ruminal volatile fatty acids were not affected by limestone level; however, rumen ammonia concentrations decreased linearly (P less than .05) with increasing limestone level. In trial 2, 12 wether lambs (avg wt 43.3 kg) were fed a 35% concentrate diet with .1, 1.5 or 3.0% limestone (.5, 1.2 and 1.6% dietary Ca, respectively) in a completely randomized design. Dry matter intake was not affected by limestone level, but digestibility of dry matter, organic matter and starch (P less than .10), energy, crude protein, acid detergent fiber (ADF) and cellulose (P less than .05) responded quadratically to limestone level, with increases at the 1.5% limestone level. Ruminal dry and organic matter (P less than .05), NDF (P less than .10), ADF (P less than .01), cellulose (P less than .05) and starch (P less than .05) digestion responded quadratically to limestone level with higher values at the 1.5% limestone level. Proportions of ruminal propionate increased linearly (P less than .01) with increasing limestone level and acetate: propionate ratio declined linearly (P less than .01) with limestone level.

Millet and alfalfa hays alone and in combination with high-energy diet for receiving stressed calves.

Calves subjected to stresses of weaning, marketing, shipping and processing ate more feed, gained more weight and gained more efficiently when fed a 75% concentrate receiving diet, alone or with free choice hay, than when fed hay alone (P less than .01). Diets with greater bulk or lower energy densities did not promote higher feed intake in these stressed calves, as would be the case in unstressed animals. No differences due to receiving diets were observed in number of calves treated, days treated per sick calf, death loss or relapses. There was a trend (P less than .1) for calves on hay diets to have fewer total sick days than those fed a 75% concentrate diet alone or with free choice hay. Feed intake, weight gains and conversion of feed to gain for calves on alfalfa hay alone were superior (P less than .05) to the corresponding measures for calves on millet hay alone. Both hays fed alone were inferior (P less than .01) to a 75% concentrate diet alone or in combination with either hay in promoting weight gains and conversion of feed to gain. Gastrointestinal tract fill estimated from apparent and predicted gains amounted to 93 and 76% of apparent gains for calves fed millet or alfalfa hay respectively, but only 58% or less for those fed diets containing the 75% concentrate milled feed. Growing lambs were in negative N balance when fed millet hay alone but retained approximately 15% of N intake when fed diets containing the 75% concentrate milled feed. N retention on alfalfa hay alone was intermediate. The data indicate net tissue growth in calves fed millet hay alone is near zero during a 28-day receiving period. No differences were noted between calves receiving grubicide as a dip and those given grubicide as a pour on.