Prostaglandins: modulators of renal function and pressor resistance in chronic liver disease.

Prostaglandins may modulate renal function and play a role in the hyperreninism and angiotensin pressor resistance of chronic liver disease. To study this possibility, we evaluated 12 patients with alcoholic cirrhosis and ascites. Urine immunoassayable prostaglandin E in 5 female patients was 3.3 +/- 0.5 micrograms/day [normal, 0.3 +/- 0.1 (SE)], renin was 14.6 +/- 3.7 ng/ml.h, and aldosterone was 76 +/- 19 ng/dl. After either indomethacin (200 mg) or ibuprofen (2000 mg) for 1 day, urine immunoassayable prostaglandin E fell to 0.8 +/- 0.4 micrograms/day, renin to 8.0 +/- 2.4 ng/mol.h, and aldosterone to 54 +/- 14 ng/dl (all P less than 0.01). Pressor sensitivity increased dramatically, and creatinine clearance transiently fell from 73 +/- 10 to 32 +/- 7 cc/min (P less than 0.01). Because a primary effect on renin might explain the renal impairment, an additional study used propranolol to lower renin activity. Renal function was unaltered by propranolol. We conclude that prostaglandins play a supportive role in maintaining renal function and are involved in the hyperreninism and pressor resistance of patients with liver disease.     

Levels of (1→3)-β-D-glucan, <Emphasis Type="Italic">Candida</Emphasis> mannan and <Emphasis Type="Italic">Candida</Emphasis> DNA in serum samples of pediatric cancer patients colonized with <Emphasis Type="Italic">Candida</Emphasis>species

Background  

Surveillance cultures may be helpful in identifying patients at increased risk of developing invasive candidiasis. However, only scant information exists on the effect of Candida colonization on serum levels of diagnostic biomarkers. This prospective surveillance study determined the extent of Candida colonization among pediatric cancer patients and its possible impact on serum levels of (1-3)-β-D-glucan (BDG), Candida mannan and Candida DNA.     

Exacerbation of thrombotic events by diesel exhaust particle in mouse model of hypertension

Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15 μg/mouse) or saline. 24 h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P<0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO? was decreased, and PaCO? increased in DEP-treated HT mice compared to NT mice treated with DEP (P<0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P<0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1-1 μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25-1 μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by DEP are exacerbated by hypertension in mice. Our findings, therefore, provide a possible plausible explanation for the cardiovascular morbidity and mortality accompanying urban air pollution.     

Chemo-radiotherapy: an alternative to surgery for squamous cell carcinoma of the rectum – report of six patients and literature review

Purpose  Since 1943 [ 1 ], only 45 patients of squamous cancer of the rectum have been reported in the published reports and the largest series to date consists of 12 patients. Reports suggest that the primary treatment is surgical resection but, in the light of nonsurgical advances in the treatment of anal squamous cell carcinoma (SCC), we present a review of the literature and report six patients treated by chemoradiation therapy (CRT).
Method  A literature search was undertaken using the keywords squamous cell, epidermoid, basaloid and cloacagenic and cancer of rectum and colon to provide evidence for this discussion from studies of surgery, radiation therapy and CRT in rectal SCC. A prospective database of the Mount Vernon Cancer Centre, UK was searched from 1995 to 2005 for patients diagnosed with pure SCC of the rectum.
Results  Six patients with histologically confirmed primary SCC of the rectum were treated with primary combination chemo-radiotherapy according to protocols used for SCC of the anal canal over a 15-year period. Surgery was avoided in four, and they remain disease-free on follow-up.
Conclusions  Primary CRT, as currently utilized in anal cancer, can be extended to primary SCC of the rectum.     

Hashimoto encephalopathy responding to risperidone

This report describes a case of Hashimoto encephalopathy in an 11-year-old girl. She presented with features typical of this disorder including encephalopathy, seizures, and neuropsychiatric symptoms. Diagnosis was supported by an elevated thyroid-stimulating hormone level, a low levo-thyroxine level, and positive results for antithyroperoxidase antibody. Her response to typical treatment with levo-thyroxine was incomplete, requiring additional therapy with valproic acid and methylprednisone. Her course was further complicated by the development of acute psychosis. Treatment with risperidone was correlated with resolution of her psychosis and improvement in neuropsychiatric symptoms. Response to antipsychotic therapy has not previously been described in the pediatric population with Hashimoto encephalopathy. This case highlights the need for guidelines for the management of this rare disorder.     

Liquid chromatographic analysis of halofantrine from dosage form and its metal interaction studies

The reversed-phase high-performance liquid chromatographic method has been developed for the determination of halofantrine from dosage form in presence of losartan potassium as an internal standard. Separation was performed on a Chrompack hypersil C₁₈ (150 × 4.6 mm) analytical reversed-phase column. Mobile phase consisted of methanol–water (70:30, v/v) pH was adjusted to 3.2 with 85% orthophosphoric acid. Mobile phase was pumped at a flow rate of 0.5 mL min⁻¹ and UV detection was performed at 248 nm. The method was validated for linearity, precision, accuracy and specificity. The linearity was observed in the concentration range 1.0–50 μg mL⁻¹ with correlation coefficient (r ²) of 0.9998. Accuracy was ranged 98–100% with precision less than 1%. The limits of detection (LOD) and (LOQ) were 0.01 and 0.03 μg mL⁻¹, respectively. This method was applied to study the drug–metal (calcium, magnesium, manganese, cobalt, ferrous, ferric chromium, zinc, nickel, cadmium, iron and copper) interaction studies which were carried out at 37 °C. These studies were beneficial to determine the drug in therapeutic concentrations inside human body as well as its complexation with metal ions. The proposed method is rapid, accurate, economical and selective because of its sensitivity and reproducibility.     

p38 Mitogen-Activated protein kinase mediates dual role of ultraviolet B radiation in induction of maturation and apoptosis of monocyte-derived dendritic cells

Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DC), for example, Langerhans cells (LC), it also stimulates some LC into maturation after irradiation in vivo. To analyze its reciprocal effects on DC, we elucidated the direct effect of UVB on DC in vitro using human monocyte-derived DC (MoDC). UVB from 50 to 200 J per m2 stimulated the maturation of MoDC with (1) augmented expression of CD86 and HLA-DR, (2) enhanced production of IL-1beta, IL-6, IL-8, and TNF-alpha at both the mRNA and protein levels, and (3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDC after UVB demonstrated a concentration-dependent phosphorylation of p38- and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPK), but not that of extracellular signal-regulated kinases. p38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDC. Interestingly, MoDC that had undergone apoptosis exhibited an augmented expression of HLA-DR without upregulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDC, depending on the dosage, via p38 MAPK pathway.