Effect of melatonin on some bone turnover markers in ovarectomized rats

This study was carried out to evaluate the effect and the mechanism of action of melatonin on some bone markers in ovarectomized bone loss in rats. 32 female albino rats underwent either bilateral laparotomy [sham, n=8] or bilateral ovarectomy [Ovx, n=24]. The Ovx rats were divided into 3 groups, each of 8 rats; Vehicle-treated [Ovx], estrogen-treated [E2] and melatonin-treated [Mlt] group. After 14 weeks treatment, blood and urine were collected. Serum osteoprotegerin [OPG], inhibin, follistatin, and alkaline phosphatase [ALPase] were determined as bone markers. In addition, urinary Deoxypyridinoline [uDPD] was assayed. Serum OPG, inhibin and follistatin levels significantly decreased upon Ovx. They increased upon either treatment with E2 or Mlt with non- significant difference in between as compared to Ovx group. In addition, serum ALPase and uDPD significantly increased on Ovx and decreased with either therapy as compared to Ovx one with non- significant difference between both therapies. The results revealed that administration of Mlt inhibited high bone turnover and prevented calcium loss in ovarectomized rats. This may be through increasing OPG, inhibin and/or follistatin levels. Mlt could be a candidate for the treatment of postmenopausal osteoporosis

Modification of angiogenesis factors in cancer patients under bisphosphonate

Recently, new experimental data suggested that, besides inhibiting osteoclasts, bisphosphonate may also have an antitumor effect. Antiangiogenic activity is one of the possible mechanisms of anticancer activity attributed to zoledronic acid; an amino-bisphosphonate. The aim of this study was to evaluate the modifications in angiogenic cytokines levels after zoledronic acid infusion. Sixteen cancer patients with bone metastases were intravenously infused with zoledronic acid. They were evaluated prospectively for circulating levels of calcium, vascular endothelial growth factor [VEGF], transforming growth factor beta1 [TGF-beta1] and interferon-gamma [IFN-gamma] at different time points: just before and after 1 and 7 days of zoledronic acid infusion. Basal VEGF serum levels were decreased significantly on the 1[st] and 7[th] day after zoledronic acid infusion, more pronounced on the 7[th] day. TGF-beta1 serum levels were significantly decreased on the 7[th] day of infusion, while IFN-gamma serum levels were significantly increased 1 day after the infusion. Moreover, the present data showed a statistically significant negative correlation between serum levels of VEGF and of both TGF-beta1 on the 7[th] day of infusion and IFN-gamma on the 1[st] day. This study confirms that the amino-bisphosphonate; zoledronic acid appears to modulate serum levels of proangiogenic growth factors such as VEGF, TGF-beta1 and IFN-gamma in cancer patients. It may have antiangiogenic properties through a significant and lasting decrease in serum levels of VEGF and TGF-beta1. In addition, it may activate the gamma delta T cell population as evidenced by increased INF-gamma level, which shows potential cytotoxic activity toward a broad spectrum of tumors

Physiopathologic role of plasma homocysteine concentration, folic acid and vitamin B[12] levels in patients with thrombotic stroke: relation to helicobacter pylori infection

To establish the link between serum homocysteine [Hcyst], folic acid and vitamin B[12] levels and Helicobacter pylori [H pylori] infection in the pathogenesis of thrombotic cerebrovascular stroke [CVS]. Subjects and Fourty patients with thrombotic CVS were selected at the Main Alexandria Hospital compared with 10 healthy subjects of matched age as a control group. Serum folate, vitamin B[12] and total Hcyst levels were determined. Also, serum anti-H pylori IgG was estimated in all included subjects. in thrombotic stroke patients; both serum folic acid and B[12] levels were significantly decreased while serum Hcyst level was significantly elevated compared to controls. Patients with hyper homocysteinemia [> 15 micro mol/l] had significantly lower levels of serum folate and vitamin B[12] and significantly higher levels of H pylori IgG than patients with normal serum Hcyst level. Serum Hcyst in stroke patients was significantly positively correlated to H pylori IgG levels and inversely correlated to serum folate and vitamin B[12]. Also, H pylori IgG level was significantly inversely correlated to serum folate and vitamin B[12]. H pylori infection may decrease serum folate and vitamin B[12] levels possibly through impairment of their absorption. This could lead to hyperhomocysteinemia due to abnormal Hcyst metabolism. Hcyst is toxic to endothelial cells and results in atherothrombosis and its sequelae

Interleukin-6 and nitric oxide synthase, myeloperoxidase and glutathione peroxidase activities in experimental model of renal ischemia-reperfusion

The aim of the present study was to evaluate the effects of L-arginine [L-Arg; nitric oxide synthase [NOS] substrate] and N[W]- nitro-L-arginine methyl ester [L-NAME; predominantly cNOS inhibitor] on renal dysfunction, inflammatory response, cellular injury and oxidative stress induced by renal I/R in rats. The study was carried out on 40 male Sprague- Dawley rats. They were divided into 4 groups as follows: Group I [control- I/R group]; 10 rats received 0.9% saline. Group II [L-Arg group]: 11 rats received L-Arg. Group III [L-NAME group]: 9 rats received L-NAME. Group IV: 10 rats as control-sham operated group for functional baseline values. Substances were injected intraperitonealy 30 minutes preoperatively. Left renal ischemia-reperfusion plus right nephrectomy were done. While control- sham group underwent right nephrectomy only. Renal function tests; glomerular filtration rate [GFR] and urinary excretion of sodium [UENa] and serum interleukin-6 [IL-6] as inflammatory marker were estimated on 7[th] day post-operatively. Renal NOS activity and glutathione peroxidase [GPx] as antioxidant enzyme were measured. Carbonyl content as a measure of oxidative protein damage and myeloperoxidase [MPO] activity as a measure of neutrophilic infiltration were assessed in both left I-R kidneys and right ones in all groups. Multiple comparisons between all groups and between left and right kidneys were performed. GFR decreased while UENa increased in all groups compared to control-sham one on 7[th] day of I/R. Serum IL-6 showed significant increase only in L-Arg I/R group [GII] as compared to the other three groups. On comparing left I/R kidneys with right ones in all groups, there was significant elevation in NOS activity in control I/R group [GI] and L-Arg group [GII]. There was decreased GPx at left I/R kidneys which was statistically significant in L-Arg group [GII] and L-NAME group [GIII]. As regards carbonyl content and MPO activity, there was significant increase in left I/R kidneys in GI and GIII as compared to right ones. While, there were significantly decreased levels in GII. Left I/R renal NOS showed positive correlation with GFR and IL-6. While, it was negatively correlated with GPx, carbonyl content, MPO, UENa and MAP. Serum IL-6 was directly correlated to GFR. L-Arginine/NO pathway seems to have a partially protective effect on kidney after I/R induced injury in rats, while L-NAME abolishes this improvement. The cNOS activity is suggested to be more involved in cytoprotection. These results need to be confirmed by studies in human beings

Autoimmune Thyroiditis is in type I versus type 2 diabetics

to determine the prevalence of autoimmune thyroiditis [AIT] as evidenced by thyroid peroxidase antibodies [TPO-ABs] in both types of diabetes Seventy five subjects from the Main Alexandria University Hospital were selected and divided into 3 groups. Group I included 30 type 1 diabetics. Group II included 30 type 2 diabetics, while group III included 15 healthy subjects of matched age and sex. Thorough history taking and physical examination were done. Fasting plasma glucose [FPG] and glycated haemoglobin [HbA1c] were estimated the following parameters were measured in serum: TPO-ABs, tyrosine phosphate-like proteins antibodies [IA2-ABs] and glutamic acid decarboxylase antibodies [GAD-ABs], Also, thyroid stimulating hormone [TSH] and free thyroxine [FT4 levels were measured in all subjects. Type l diabetics had the highest frequency of TPO-ABs positivity [26.7%], while in type 2, it was 10% vs control 6.7%, but it did not reach significant levels. TPO-ABs positivity was significantly associated with higher levels of IA2-ABs and GAD-ABs. It was also significantly associated with elevated TSH levels and insignificantly related to low free T4 levels. Conclusions: AIT, as evidenced by TPO-Abs, was present in type 1 diabetics and some type 2 with late life onset [LADA], a/though it did not reach significant levels. Results obtained were encouraging for diabetes and AIT prediction and for immunointervention measures to be used in high risk subjects