Interactions of herbicides 2,4-D and dinoseb with liver mitochondrial bioenergetics

The use of drugs for common pregnancy complications like premature labor, hypertensive diseases, and premature rupture of membranes with chorioamnionitis is reviewed. In addition, new publications on antiviral drugs in HIV-positive pregnant patients are also discussed. Among the drugs, suppressing premature labor side-effects of beta-mimetics are of growing concern. The effectiveness of other agents like magnesium, indomethacin, and sulindac are addressed. The various mechanisms explaining the beneficial effect of magnesium in pre-eclampsia are reviewed and new data on antihypertensives, such as labetalol, calcium channel blockers, and methyldopa are presented. The evidence from various clinical trials on the value of low-dose aspirin as a prophylactic agent against pregnancy-induced hypertension, pre-eclampsia, and intrauterine growth retardation in high-risk and low-risk patients is compared. Pharmacokinetic data including transplacental transfer of antibiotics and anti-HIV nucleosides are part of this review.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.     

Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Ultrastructural and immunocytochemical features of a case of neuroendocrine carcinoma developing in a prior ileostomy site

A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at the site of a previous long-standing ileostomy is reported. The neuroendocrine features are documented by both ultrastructural and immunocytochemical findings. Carcinoma arising in an ileostomy site is rare but has been recorded in patients with long-standing ileostomies after colectomy for chronic inflammatory bowel disease, as in this patient. Neuroendocrine carcinoma developing in this setting apparently has not been described before, however.     

Progressive scoliosis with vertebral rotation after lumbar intervertebral disc herniation in a 10-year-old girl

A case report of a 10-year old girl with a herniated disc is presented. The most significant symptoms were progressive scoliosis with a flat back and paravertebral muscle spasm. An absent H reflex on the left and an increased latency of the somatosensory-evoked potentials of the left posterior tibial nerve were found. The computed tomographic scan of the lumbar spine showed a large central left-sided disc protrusion at the L5-S1 level. Our case presents the youngest patient with documented intervertebral disc herniation and the only one with severe scoliosis and vertebral rotation. The curve was not structural because it improved with surgery and an orthosis was not necessary.     

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.     

Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes

In this report, the role of 34 kDa HA-binding protein in hyaluronic acid-induced cellular signalling in lymphocytes has been examined. The binding of 125I-HA to lymphocytes in vivo was found to be inhibited by pre-incubation of the cells with anti-34 kDa HA-binding protein antibodies, thus confirming 34 kDa HA-binding protein as the specific HA-receptor in lymphocytes. This observation was substantiated by anti-34 kDa HA-binding protein antibodies immunoblotting and 125I-HA ligand blotting of lymphocytes cell lysate. The HA-induced cell aggregation, tyrosine phosphorylation and cytoskeletal protein phosphorylation demonstrate the HA-induced early cellular signalling events in lymphocytes. Further, to study the involvement of 34 kDa HA-binding protein in mitogen induced lymphocyte signalling, we studied in vivo phosphorylation and secondary messenger formation. The enhanced 34 kDa HA-binding protein phosphorylation by HA and the inhibition of cellular aggregation and IP3 formation by anti-HA-binding protein antibodies revealed that 34 kDa HA-binding protein is one of the potential mediators in HA-induced signal transduction.