Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer cells

Vitamin D and its analogues are potent regulators of cell growth and differentiation both in vivo and in vitro. We studied the effects of 25-hydroxyvitamin D(3) [25(OH)D(3)], 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes 24-hydroxylase (24OHase) and 1alpha-hydroxylase (1alphaOHase). Our results showed that high concentrations (10 and 100 nM) of 1,25(OH)(2)D(3) inhibited a cell proliferation, whereas low concentration (0.1 nM) stimulated growth of the OVCAR-3 cells. In the concentration range of 10-500 nM a prohormone, 25(OH)D(3), stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)(2)D(3) inhibited growth with an equal magnitude. The expression of 24OHase was strongly induced by 1,25(OH)(2)D(3) and EB 1089 in OVCAR-3 cells, and analysis of vitamin D metabolites showed the functionality of 24OHase. An inhibition of 24OHase activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of 1,25(OH)(2)D(3) and suppressed the growth stimulation of 100 nM 25(OH)D(3). We also report the expression of a vitamin D activating enzyme, 1alphaOHase, in 7 ovarian cancer cell lines. The production of 1,25(OH)(2)D(3) in OVCAR-3 cells was low, possibly due to an extensive activity of 24OHase or a low 1alphaOHase activity. These results suggest that in ovarian cancer cells vitamin D metabolizing enzymes might play a key role in modulating the growth response to vitamin D. The possible mitogenic effects of vitamin D should be considered when evaluating treatment of ovarian cancer with vitamin D.     

No variants in the cardiac actin gene in Finnish patients with dilated or hypertrophic cardiomyopathy

Background Dilated and hypertrophic cardiomyopathies are primary myocardial diseases that cause considerable morbidity and mortality. Although these cardiomyopathies are clinically heterogeneous, genetic factors play an important role in their etiology and pathogenesis. The defects in the cardiac actin (ACTC) gene can cause both cardiomyopathies. The aim of our study was to screen for variants in the ACTC gene in patients with dilated or hypertrophic cardiomyopathy from Eastern Finland. Materials and Methods Altogether, 32 patients with dilated and 40 patients with hypertrophic cardiomyopathy were included in the study. Commonly approved diagnostic criteria were applied, and secondary cardiomyopathies were carefully excluded. All 6 exons of the ACTC gene were amplified with polymerase chain reaction and screened for variants with single-strand conformation polymorphism analysis. Results and Conclusion We did not find any new or previously reported variants. Our results indicate that defects in the ACTC gene do not explain dilated cardiomyopathy or hypertrophic cardiomyopathy in subjects from Eastern Finland and confirm earlier results that the ACTC gene does not play an important role in the genetics of dilated or hypertrophic cardiomyopathies. (Am Heart J 2002;143:11-4.)     

The fixation properties of carbon fiber-reinforced liquid crystalline polymer implant in bone: an experimental study in rabbits

A novel composite material with ultra-high strength and a low elastic modulus called carbon fiber-reinforced liquid crystalline polymer (LCP/CF) has been developed. We studied the fixation properties of an intramedullary LCP/CF rod in rabbit bone. The medullary canals of both femora were reamed with a drill 3.2 mm in diameter starting from the trochanteric fossa in eleven New Zealand White rabbits weighing on average 4.8 kg. A smooth LCP/CF rod 3.2 mm in diameter and 50 mm in length was introduced into the medullary canal of both femora. The follow-up intervals were 0, 6, 12, and 52 weeks. The upper part of the harvested femora was cut into two pieces, each 25 mm in length. A mechanical push-out test was performed within 48 h to determine bone-implant interface attachment strength in the proximal (cancellous) and distal (cortical) locations. The mean push-out strength values at 0, 6, 12, and 52 weeks were 61, 250, 382, and 612 KPa in the cancellous location and 0, 32, 41, and 68 KPa in the cortical location, respectively. The strength of the bone/implant interface appeared to be quite low, similar to other uncoated or nonporous implants, but it was found to increase with time.     

Familial hypercholesterolaemia in Finland: common, rare and mild mutations of the LDL receptor and their clinical consequences. Finnish FH-group

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) receptor which occur in heterozygous form in approximately one in 500 individuals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol levels, accelerated development of atherosclerotic vascular disease, and, if untreated, shortened lifespan. The Finnish population, which represents a genetic isolate, offers exceptional possibilities for genetic-epidemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum of genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations inhibiting cholesterol absorption for the modern treatment of FH.     

Study of the Impact of Deltamethrin Impregnated Mosquito Nets on Malaria Incidence at a Military Station

Deltamethrin impregnated mosquito nets have been successfully used all over the world to combat malaria. To study the efficacy of these mosquito nets in the service conditions of Armed Forces, a field trial of Deltamethrin impregnated mosquito nets was carried out at Military Stations ‘A’ (trial station) and B (control station) between July 96 to June 99. July 96-June 97 was the pretrial year during which base line data was collected for malaria incidence. Three rounds of Deltamethrin impregnation of the mosquito nets were done in the trial station for the actual trial duration (July 97-June 99) in lieu of residual spraying. Antimalaria measures including residual spray were continued as usual in the control station. The intervention led to a significant decline in slide positivity rate and malaria incidence in the trial station. Malaria cases declined by 87% in the trial station whereas the control station noticed an increase by 75% at the end of the trial.Key Words: Deltamethrin impregnated mosquito nets, Malaria control     

Chromatin condensation during glutamate-induced excitotoxicity of cerebellar [correction of celebellar] granule neurons precedes disintegration of nuclear DNA into high molecular weight DNA fragments

The disturbance of the intracellular ionic homeostasis after activation of channel-associated membrane receptors by the excitatory neurotransmitters represents a principle event that triggers excitotoxic cell death of neurons. Here we demonstrate that glutamate-induced excitotoxicity of cerebellar granule neurons was accompanied by apoptosis-like nuclear shrinkage, chromatin condensation, and disintegration of nuclear DNA into high molecular weight DNA fragments, but was neither associated with activation of caspase 1, -2, -3, -9, nor was protected by a pan-caspase inhibitor, zVAD-fmk. We further demonstrate that chromatin condensation took place at the early stages of excitotoxicity and preceded nuclear DNA fragmentation. The results suggest that fragmentation of nuclear DNA and condensation of chromatin are uncoupled events during neuronal cell death