Role of nigella sativa oil, thymoquinone with and without pyrimethamine in freund's adjuvant arthritis in rat

Nigella sativa oil and its active principal thymoquinone have been screened for their beneficialeffects that had been attributed to their cytoprotective, antioxidant actions and to their effect on many mediators ofinflammation. Similarly, pyrimethamine [PY], which is well known for its anti-parasitic action for a long time, hasbeen reported to have immunomodulating and apoptotic activities. The aim of the present study was to investigate the effect of Nigella sativa oil [NSO] andthymoquinone [TQ] in Freund's adjuvant arthritis [AA] in rats, an immunological experimental model of arthritiseither by sole administration of each of them or by their combination with pyrimethamine. The pain response and polyarthritis index were scored. Certain biochemical markers of inflammation,namely, interleukin-6 [IL-6], leukotriene B[4][LTB[4]], Matrix metalloproteinase-9 [MMP-9] were measured.Oxidative stress indices; reduced glutathione [GSH], erythrocytic superoxide dismutase [SOD] activity andmalondialdehyde [MDA] were also assayed in the sera of studied rats. The study demonstrated secondary inflammatory reactions in adjuvant arthritic rats [AA] as compared tothe control non- arthritic group. The study also revealed significant suppression of these secondary inflammatoryreactions as guided by reduction in the mean values of both polyarthritis index and pain response score in AA-treated rats. Significant reduction in IL-6, LTB[4], MMP-9 in the serum of treated groups was observed. This wasaccompanied with a significant increase in GSH serum level together with reduction of MDA levels in the treatedgroups. SOD activity did not change with the observed protection obtained by the studied drugs. PY + TQ, then PY + NSO, TQ and lastly NSO had reduced secondary reaction to Freund's adjuvantinoculation when used in the day of inoculation up to 20 days. It can be also concluded that combination with PYenhanced the chemoprotective effects of both TQ and NSO. Further experimental and clinical trials have to bedone for further screening of such combinations

possible reno- and vascufoprotective of drugs that inhibit the renin angiotensin system in diabetic rats

Aim: The renin angiotensin system [RAS] plays an important role in the development of diabetic renovascular pathology characteristic of diabetic nephropathy [DN]. Through inhibition of RAS by different mechanisms, angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II type 1 receptor blockers [ARBs] could slow the progression of diabetic renovascular disease. Thus, the present study was undertaken to test the hypothesis that a combination of an ACEI [fosinopril] and an ARB [candesartan] could exert additive reno- and vasculoprotective effects in uninephrectomized [UNE], streptozotocin [STZ] -induced diabetic rats. Material and Fifty male albino rats weighing 150-200 g were used in the present study. Rats were divided into five groups [each of ten rats]; ten rats of them were taken as normal sham-operated group. The remaining forty rats were subjected to left unilateral nephrectomy and then three weeks later, diabetes was induced by a single intravenous injection of STZ. The UNE STZ - diabetic rats were further subdivided into: control rats that were given no additional treatment but insulin s.c., UNE STZ -diabetic rats treated with fosinopril in addition to insulin for 16 weeks, UNE STZ - diabetic rats treated with candesartan in addition to insulin for 16 weeks and the fifth group was UNE STZ -diabetic rats treated with a combination of fosinopril and candesartan in addition to insulin for 16 weeks. UNE STZ - diabetic rats exhibited the characteristic features of diabetic renal disease including increased BP, plasma creatinine [PCr], urinary albumin excretion [UAE], kidney weight [KW], BG and glycosylated hemoglobin [HbAIc] together with decreased urinary creatinine [UCr] and creatinine clearance [CrCI]. Furthermore, control rats showed significant elevations in plasma transforming growth factor-beta 1 [TGF-D 1] and in renal malondialdehyde [MDA] associated with significant reduction in renal reduced glutathione [GSH]. Edothalial dysfunction [ED] of renal arteries isolated from STZ-diabetic rats, evidenced by a significant decrease in percentage of maximal relaxation in response to acetylcholine [ACH], has been also demonstrated. Oral administration of fosinopril or candesartan for 16 weeks in UNE STZ diabetic rats produced significant decreases in KW,BP, PCr,UAE, plasma TGED1 and renal MDA concentration together with significant increase in UCr, CrC 1 and renal GSH concentration. Vasculoprotective effect of fosinopril and candesartan has been also found, evidenced by a significant increase in the percentage of maximal relaxation in response to Ach in renal arteries isolated from UNR STZ-diabetic rats treated with fosinopril or candesartan Treatment of UNE diabetic rats with a combination of an ACEI [Fosinopril] and an ARB [candesartan] improved most of the estimated biochemical parameters as well as BP more significantly than either drug alone, but the combination of both drugs did not result in a significant difference in the percentage of maximal relaxation in response to Ach in renal arteries compared to either drug given alone. Conclusions: the results of the present study demonstrated that ACEIs and ARBs have a comparable degree of reno- and vasculoprotection in UNE STZ- induced diabetic rats Moreover, the present study demonstrated an additive renoprotective effect of combination therapy with ACEIs and ARBs over monotherapy with either class alone

Methanol poisoning: clinical manifestations, investigations, formic acid level, management, and outcome

The present work was carried out to study patients with acute methanol poisoning as regards severity of clinical manifestations, laboratory investigations, formic acid level and management and to correlate these with the outcome. The study included twenty patients diagnosed as acute methanol poisoning following consumption of wine. They were admitted to Alexandria Poison Center [APC] and critical care medicine department at Alexandria Main University Hospital during four months period [February-May] in the year 2001. Patients were interviewed and clinically examined. Blood samples were collected immediately after admission for estimation of serum formate, blood gases and acid-base status. Also, brain computed tomography scanning [CT] was done. The results revealed that acute methanol poisoning is more common in young age group from 15-35 years [70.0%]. The longer the latent period i.e. the time lapsed since intake of methyl alcohol and appearance of symptoms, the lowest were the pH and bicarbonate levels, the highest was serum formate level and the worst was the CT and outcome

Steriod microdose therapy in rheumatoid arthritis patients: impact on bone metabolism

The anti-inflammatory and immuno-suppressive properties of GCs have prompted their extensive use in the management of various diseases including RA. However, the benefits derived from the use of GCs may be offset by the occurrence of GCs related side effects. One of the most important side effects of long-term use of GCs is osteoporosis. Steroid microdose therapy [simply called Microdose Therapy], a university-spin-off technology, is a physician-supervised, 3-step, education program for teaching patient control of GCs for controlling chronic inflammation in arthritic patients. This Microdose Therapy uses very low dose of prednisone [

Effect of some drugs with immunosuppressive properties on IgE mediated mast cell degranulation and delayed type hypersensitivity

This study was carried out on 60 adult albino rats and 30 mice of cyclosporin A [CsA], methotrexate [MTX], ribavirin and dexamethasone [Dxt] on peritoneal mast cell [PMC] histamine release, passive cutaneous anaphylaxis [PCA] reactions in rats and DTH in mice. The studied animals were divided into three groups: The first was to study the effect of previous drugs on PMC histamine release in actively sensitized rats, the second was to study the effect of previous drugs on PCA in passively sensitized rats and the third was to study the effect of previous drugs on the induction of DTH in mice in vivo. Each group was divided into five subgroups and were pretreated with saline [control] or one of the previously mentioned drugs