Mammography phototimer technique chart

A phototimer technique chart for mammography is presented along with the methodology used to design it. The chart is based on accurate measurement of breast thickness and helps overcome the inability of the phototimer to track as breast thickness varies. In clinical practice, the chart results in the consistent attainment of optimally exposed films and decreased number of retakes.     

Cerebral blood flow increases evoked by electrical stimulation of rat cerebellar cortex: relation to excitatory synaptic activity and nitric oxide synthesis

The purpose of this study was to examine mechanisms involved in the coupling of neuronal activity to cerebral blood flow (CBF). CBF was measured in rat cerebellum using laser-Doppler flowmetry during stimulus-evoked neuronal activity and related to the distribution of the extracellular field potential. Local electrical stimulation of the cerebellar cortex activated a narrow beam of parallel fibers (PFs) 100 μm across and evoked increases of CBF along (On-B) and perpendicular (Off-B) to the beam. Increases of CBF and field potentials were recorded for a distance of up to 1500 μm along the activated beam, and perpendicular to the beam, in a zone approximately 1000 μm wide, i.e. about 10 times wider than the zone in which synaptic excitation took place. CBF increased as a function of stimulus frequency up to 75 Hz, the response being larger On-B than Off-B. TTX abolished both the field potentials and the CBF responses at all frequencies, suggesting that action potentials were mechanistically related to the evoked CBF increases. CBF changes were unchanged by picrotoxin, a blocker of GABA_A receptors, consistent with the idea that inhibitory synaptic activity does not contribute to CBF increases. The latency to the CBF rise was much shorter On-B than Off-B for the same distance from the stimulating electrode. This may suggest that the CBF response Off-B is dependent on diffusion of vasoactive substances from neuronal structures activated by the parallel fibers On-B. Nitric oxide (NO) synthase inhibition withN^G-nitro-l-Arginine increased the time latency to onset of CBF rise by 2–4 times and attenuated the evoked CBF increase by approximately 50%. Sodium nitroprusside, a NO donor, increased baseline CBF, but did not reverse the effects ofl-NNA. Thus the initial part of the evoked CBF rise is probably mediated by NO, which also contributes to the later part of the response. This study provides insight into the distribution and mechanism of neurally evoked increases of CBF, of putative importance for the interpretation of activation studies in animals and humans.     

A model for determining the effect of mammography service screening

In an overview, Swedish mammography screening trials demonstrated a 29% reduction in breast cancer mortality in women aged 50-69 and no effect on total mortality. Three Danish regions introduced mammography screening in the 1990s. The authors developed a method to evaluate the effect of mammography service screening on breast cancer mortality and validated it applying it to total mortality, where no effect was expected. Study groups and historical and national control groups were analysed using Poisson regression. Total mortality in the screening regions and periods was close to that expected in the absence of screening. A small (3%) excess risk, also seen in a non-screening area, probably results from regional differences changing over time. The effect of this is inseparable from the screening effect. The design is adequate for analysing the effect of mammography service screening on breast cancer mortality.     

Dysgenesis and Histological Changes of Genitals and Perturbations of Gene Expression in Male Rats after In Utero Exposure to Antiandrogen Mixtures

We investigated the ability of a mixture of three androgen receptorantagonists to induce disruption of male sexual differentiationafter perinatal exposure. The aim was to assess whether thejoint effects of vinclozolin, flutamide, and procymidone canbe predicted based on dose-response data of the individual chemicals.Chemicals were administered orally to pregnant Wistar rats fromgestational day 7 to postnatal day 16. Changes in reproductiveorgan weights and of androgen-regulated gene expression in prostatesfrom male rat pups were chosen as end points for extensive dose-responsestudies. With all end points, the joint effects of the threeantiandrogens were dose additive. Histological evaluations showedthat dysgenesis and hypoplasia of prostates, seminal vesicles,and epididymis were seen with the highest mixture doses. Nochanges were observed in any single-compound low-dose groupfor these lesions, nor were there histopathological changesin the testes. Pronounced dysgenesis of external genitals wasobserved with all doses of the mixture, and severe dysgenesiswas seen with a mixture for which the individual compounds causedno effects. A combination of doses of each chemical that onits own did not produce significant reductions in the weightsof seminal vesicles and PBP C3 expression induced a marked mixtureeffect. Thus, antiandrogens cause additive effects on end pointsof various molecular complexities such as alterations at themorphological and the molecular level. Exposure to antiandrogens,which appears to exert only small effects when judged on a chemical-by-chemicalbasis, may induce marked responses in concert with, possiblyunrecognized, similarly acting chemicals.     

Trefoil factors are expressed in human and rat endocrine pancreas: differential regulation by growth hormone

Trefoil factors (TFFs) 1, 2, and 3 are expressed in mucosal epithelia. TFFs are particular abundant in the intestine in which they play a crucial role in maintenance and restitution of the epithelium. Because pancreas developmentally arises from the primitive foregut, we explored the expression of TFFs in the pancreas in man and rat. Immunocytochemical staining of adult human pancreas showed abundant TFF3 immunoreactivity in pancreatic islets and some duct cells, whereas weak TFF1 and no TFF2 staining were detected. In the islets TFF3 localized to most insulin and some glucagon and pancreatic polypeptide-producing cells. TFF3 immunoreactivity was colocalized with insulin and glucagon in distinct cell clusters in human fetal pancreas at wk 14 and in the newborn rat pancreas. In isolated human and rat islets, TFF3 and TFF1 mRNA was identified by RT-PCR, and TFF3 protein was detected in human pancreas and islets by ELISA. Exposure of neonatal rat islets or insulinoma cells to GH, a known beta-cell growth factor, resulted in markedly increased TFF3 but decreased TFF1 mRNA levels. The effect of GH on TFF3 expression was confirmed by Western blot. Culture of neonatal rat islets in the presence of TFF3 resulted in attachment and migration of the islet cells, but no effects on proliferation, insulin secretion or cytokine-induced apoptosis were seen. These data demonstrate expression of TFFs in the endocrine pancreas, but their possible functions remain unknown.     

Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania

Two main haplotypes, CVIET and SVMNT, of the Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt) are linked to 4-aminoquinoline resistance. The CVIET haplotype has been reported in most malaria-endemic regions, whereas the SVMNT haplotype has only been found outside Africa. We investigated Pfcrt haplotype frequencies in Korogwe District, Tanzania, in 2003 and 2004. The SVMNT haplotype was not detected in 2003 but was found in 19% of infected individuals in 2004. Amodiaquine use has increased in the region. The introduction and high prevalence of the SVMNT haplotype may reflect this and may raise concern regarding the use of amodiaquine in artemisinin-based combination therapies in Africa.     

OXIDATIVE DNA DAMAGE IN MALE WISTAR RATS EXPOSED TO DI- n -BUTYL PHTHALATE

Dialkyl phthalate esters are used in the plastic industry and widely distributed in the environment. Previously, it has been shown that di- n -butyl phthalate (DBP) produces testicular atrophy and liver enlargement in rodents, and the mechanisms behind this could involve reactive oxygen species (ROS). In this study, oxidative DNA damage was measured in terms of the premutagenic modified nucleoside 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in nuclear DNA from liver, kidneys, and testes from rats exposed to DBP in the perinatal or preadult period. In one experiment, pregnant rats were administered 0 or 0.5 g DBP/kg/d by gavage from d 7 after conception to d 17 after delivery and organs from male offspring were analyzed. In a second experiment, 25-d-old rats were administered 0, 0.5, or 2 g DBP/kg/d by gavage for 10 d. After perinatal exposure, body and organ weights were unchanged. The 8-oxodG/10 6 dG ratio in liver DNA increased significantly in the exposed group. In contrast, the 8-oxodG/10 6 dG ratio was significantly decreased in kidney DNA, whereas it remained unchanged in the testis. After preadult exposure (postnatal d 25 to 34) the testes weight of the exposed animals were significantly decreased and severe atrophy of the seminiferous tubules was observed. The body weight of the animals in the high-dose group was significantly decreased compared to the control. The 8-oxodG levels in liver, kidney, and testis DNA remained unchanged. Although ROS has been suspected of being involved in the formation of testicular atrophy in phthalate-exposed rats, no apparent sign of oxidative DNA damage was found after phthalate exposure perinatally or during the preadult stage. With respect to phthalate-induced oxidative DNA damage in the liver, it appears that the developmental stage during exposure is important.