Platelet and neutrophil cross-talk-mediating cancer growth and metastasis in patients with urinary bladder cancer

The initial selectin-dependent events that mediate tumor cell tethering to platelets, leukocytes, and vascular endothelium can regulate the extravasation and colonization of metastatic cells into distant tissues. We aimed to clarify the role of selectin-selectin ligand interactions in tumor growth and progression in patients with bladder cancer. Thirty patients with bladder cancer were the participants in this study classified as follows: locally invasive group [n = 10], urinary bladder cancer group with regional lymph node involvement [n = 10], and urinary bladder cancer group with regional lymph nodes and distant metastasis [n = 10]. Flow cytometry was used to determine both the platelet surface expression of P-selectin [CD62P] and the neutrophil surface expression of PSGL-1 [CD162], whereas enzyme-linked immunosorbent assay was used for the assay of soluble P-selectin. Neutrophil PSGL-1 expression among the different groups studied was not statistically significant. However, there was enhanced platelet activation as evidenced by increased platelet surface expression of P-selectin together with an increase in its soluble form, which was more prominent with advancement of the disease, especially in patients with distant metastasis. Also, a strong positive correlation was found between platelet P-selectin and its soluble form with the tumor grading. In addition, stepwise multiple regression analysis showed that both P-selectin and platelet count are significant independent determinants for the stage of bladder cancer, suggesting augmentation of P-selectin-ligand interaction. These data preclude that disease progression in patients with bladder cancer is dependent on the complex interaction between P-selectin and its ligand. Targeting of these molecules may represent a unique approach to tumor therapy and prevention of metastasis

Assessment of adreno pulmonary toxicity of Dicofol in adult male albino rats

Dicofol is an organochiorine insecticide. The possible toxic effect of dicofol on the rats adrenal glands and lungs was investigated when it was given daily per oral route at two dose regimens according to LD50 for three different durations [4, 7 and 21 months]. The study was carried out on 72 adult male albino rats. They were divided into 4 main groups. Group I, the negative control group, was I subdivided into three subgroups. Group II was the 4 month duration group, which was subdivided into subgroup ha given dicofol 4.19 mg/kg daily and subgroup IIb given 16.75 mg/kg. The third group was the 7 month duration group, which was also subdivided into subgroup IIIa given the former dose and subgroup IIb given the later dose of dicofol. In the fourth group, the animals were divided into two subgroups, subgroup IVa given the former dose of dicofol for 21 months and subgroup IVb given the later dose of dicofol for the same duration. At the end of each experimental period, the animals were sacrified. Serum Nat K[+] and cortisol levels were investigated. Histopathological examination of the adrenal glands and the lungs was also carried out. The results showed that dicofol had obvious toxic effects on the adrenal glands and lungs. The toxicity was time and dose dependent. Such toxicity was in the form of an increase in the serum levels of Na[+] and K[+] in addition to decrease in serum level of cortisol. Histopathological examination of adrenal glands showed cytoplasmic vaculation in the cells of zone glomerulosa and fasiculata together with capsular thickening and haemorrhage in zona fasiculata and cortical damage. As regards the lung tissues, there were hyperplasia and lymphoid aggregation in the epithelial cells lining of the alveoli, as well as collapse and emphysema in the alveoli. Also, there were cellular infiltration, with foamy cytoplasm and large nuclei. In conclusion, prolonged administration of dicofol to adult male albino rats can affect both adrenals and lungs. Further wide-scaled experimental study is recommended

Cytoprotective effect of lithium against neuronal programmed cell death induced by carbamazepine in albino rats

Mood-regulating drugs have revolutionized the management and prognosis of manic- depressive illness. Lithium was the first mood-regulating drug to be used in 1960s and remains the most usable one. Carbomazepine [CBZ] has also proved an effective alternative drug for lithium. If neuronal programmed cell death induced either by short term or chronic CBZ intoxication and suppressed by coadministration of lithium, the later may increase the beneficial effect of CBZ by increasing this drug's efficacy/toxicity ratio. Sixty-four adult male albino rats were used in this study and classified into 5 groups as follows: Negative control group I, distilled water group II,lithium carbonate group III [IIIa and IIIb], CBZ group IV [Iva and Ivb] and the last group was combination of CBZ and lithium carbonate group V [Va and Vb]. Animal scarification was carried out after the end of the experimental period [3 days and 12 weeks, respectively]. Flow-cytometric analysis for cerebellar granule cells DNA of CBZ subgroups revealed significant elevation of abnormal DNA pattern with increase in apoptotic cell percentage. Also, caloremctric determination of DNA content showed significant increase in the DNA fragmentation percentage. Histological study also revealed typical granule cell death. These previous changes were significantly improved when lithium salt was concomittently administered with CBZ [group V]. So, the study recommended further experimental evaluation of lithium effect against other causes of neuronal apoptosis such as radiation, aging and hypokalaemia in the brain cells

protective effect of L-Carnitine, desferriox-amine, and verapamil on mitigation of Epirubicin-induced cardiomyopathy in adult albino rats

The present study was conducted on 70 adult albino rats of both sexes [180 +/- 20 g body weight] divided into nine groups: Group I [negative control group], group II [isotonic saline 0.5 ml intraperitoneal, i.p.], group III [L-carnitine 50 mg/kg i.p.], group IV [desferrioxamine 90 mg/kg i.p.], group V [verapamil 10 mg/kg i.p.], group VI [epirubicin 2.25 mg/kg i.p.], group VII [epirubicin-L- carnitine], group VIII [epirubicin-desferrioxamine] and group IX [epirubicin-verapamil]. At the end of the experimental period [12 weeks], blood pressure and heart rate were measured and blood samples were collected for investigating serum aspartate aminotransferase [AST], lactic dehydrogenase [LDH], creatine phosphokinase [CPK], creatine phosphokinase isomer [CPK MB], heart fatty acid binding protein [HFABP], glutathione peroxidase [GSH] and malondialdehyde [MDA]. Cardiac tissue samples were taken for estimating the tissue levels of MDA and GSH. Furthermore, a histopathological examination of the heart was carried out

Some of the toxic responses accompanying both short and long term administration of mycophenolate mofetil in adult albino rats

Some of the toxic hazards associated with short- and long-term administration of mycophenolate mofetil [Cellcept] were evaluated in this study. It was conducted on 36 adult albino rats of both sexes [180 +/- 20 g body weight]. They were divided into four main groups: A negative control group [group I], positive control groups [IIa and IIb] received distilled water orally and Cellcept groups [III and IV] received Cellcept 72 mg/day and 36 mg/day orally for one and three months, respectively. At the end of the study, blood samples were collected for the determination of Hb concentration, red blood cells count [RBCs], white blood cells count [WBCs] and platelets counts, blood urea nitrogen [BUN], serum creatinine, uric acid, potassium [K+], sodium [Na+] and calcium [Ca++] levels. Furthermore, a histopathological examination of the small intestine and the kidneys was carried out

role of calcium channel blockers in methyl mercury-induced neurotoxicity and nephrotoxicity in adult Albino rats

This study was carried out on 135 adult albino rats of both sexes to investigate the effect of repeated administration of methyl mercury on brain and kidney and to evaluate the possible protective role of calcium channel blockers. The rats were divided into nine equal groups. The brain and the kidneys were dissected and prepared for a light microscopical examination. The administration of methyl mercury [group VI] resulted in an affection of certain areas of the brain. The cerebellar cortex was mostly affected. The purkinje cells were shrunken with irregular outlines, while many granule cells showed pyknotic nuclei. Certain areas of the cerebral cortex were affected, especially the occipital cortex. The kidney function tests were significantly affected and histologically, both proximal and distal convoluted tubules were severely affected. In group VII and group VIII, there was a slight biochemical and histological improvement. A marked improvement was also observed in group IX. It was concluded that the use of multiple calcium channel blockers could improve neurotoxicity and nephrotoxicity induced by methyl mercury