Biochemical and hematological studies on perch, Perca fluviatilis, from the cadmium-contaminated river Emån

In a field investigation, biochemical and hematological parameters were measured in perch, Perca fluviatilis, living in the cadmium-contaminated river Emån in the southeast of Sweden. The number of lymphocytes was 45–100% higher in perch from the contaminated area than in the reference perch, indicating a stimulated immune defense. In addition, the cadmium-loaded fish suffered from a slight anemia and a disturbed carbohydrate metabolism and blood plasma ion composition. The observed effects suggest that cadmium affects fish in the environment similar to what has been observed in laboratory studies. However, the weaker response may imply that the perch in the field situation have been adapted and thus acquired an increased resistance to cadmium.     

Brain Insults in Rats Induce Increased Expression of the BDNF Gene through Differential Use of Multiple Promoters

The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.     

Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model of global cerebral ischemia

Heat shock protein 70 (Hsp70) is induced in cells by a variety of stress conditions, is known to be cytoprotective, and has been proposed to be neuroprotective during brain ischemia. A recently developed mouse model of 12-min global cerebral ischemia by bilateral common carotid artery occlusion with artificial ventilation and bilateral monitoring of regional cerebral blood flow by laser Doppler was applied. We examined the expression and possible neuroprotective role of the inducible form of Hsp70 in the mouse brain following global cerebral ischemia. Ischemia induced a marked expression of Hsp70 in the ischemia vulnerable CA1-CA3 region of the hippocampus. Intraischemic hypothermia (33°C) prevented cell damage without noticeable expression of Hsp70. A transgenic mouse overexpressing Hsp70 was subjected to 12 min of global cerebral ischemia, and the brain damage was evaluated after 4 days. No neuroprotection of ischemia-induced brain damage in hippocampus, striatum, cortex or thalamus was found in Hsp70 transgenic animals compared with wild-type littermate mice. We suggest that overexpression of Hsp70 following cerebral ischemia is an indicator of cell stress. Also, constitutively overexpression of Hsp70 is insufficient to effectively influence cell death after global cerebral ischemia in the mouse.     

Mutans streptococci colonization and longitudinal caries detection with laser fluorescence in fissures of newly erupted 1st permanent molars

OBJECTIVE: To longitudinally apply a laser fluorescence (LF) device (DIAGNOdent) in newly erupted 1st permanent molars over a 3-year period and to relate the findings to mutans streptococci (MS) colonization, fissure morphology, and caries development. MATERIAL AND METHODS: The material consisted of 101 consecutive 5 to 6-year-old children attending a Public Dental Clinic and who volunteered after ethical approval and informed consent had been given. Only fully erupted molars with clinically sound fissures were included. At baseline, the fissures were subjectively categorized as "shallow" or "deep", and, prior to the LF readings, a plaque sample was collected and cultivated for MS using a chair-side kit. The registrations were repeated annually and the microbial samplings after 2 years. The total drop-out rate was 12%. RESULTS: The mean LF values increased significantly (p<0.05) with increasing age from 8.2 to 12.4 in the teeth that remained sound. Thirty-five teeth were decayed or filled during the follow-up and their mean LF values increased from 13.4 to 40.7. The LF readings were significantly higher in molars with "deep" fissures (p<0.05) at all visits. MS colonization at baseline was associated with an increased risk for caries (OR = 11.6, p<0.05) and significantly elevated LF readings. Baseline LF readings > or =12 were not diagnostic for dentin caries or fillings over the study period (sensitivity 0.57; specificity 0.86). CONCLUSION: LF readings could be used to some extent to monitor fissure morphology and caries development in fissures of newly permanent molars over time, but elevated initial values were not predictive for caries development.     

High level PHGDH expression in breast is predominantly associated with keratin 5‐positive cell lineage independently of malignancy

We have previously reported the 2D PAGE‐based proteomic profiling of a prospective cohort of 78 triple negative breast cancer (TNBC) patients, and the establishment of a cumulative TNBC protein database. Analysis of this database identified a number of proteins as being specifically overexpressed in TNBC samples. One such protein was D‐3‐phosphoglycerate dehydrogenase (Phgdh), a candidate oncogene. We analysed expression of Phgdh in normal and TNBC mammary tissue samples by 2D gel‐based proteomics and immunohistochemistry (IHC), and show here that high‐level expression of Phgdh in mammary epithelial cells is primarily associated with cell lineage, as we found that Phgdh expression was predominant in CK5‐positive cells, normal as well as malignant, thus identifying an association of this protein with the basal phenotype. Quantitative IHC analysis of Phgdh expression in normal breast tissue showed high‐level expression of Phgdh in normal CK5‐positive mammary epithelial cells, indicating that expression of this protein was not associated with malignancy, but rather with cell lineage. However, proteomic profiling of Phgdh showed it to be expressed in two major protein forms, and that the ratio of expression between these variants was associated with malignancy. Overexpression of Phgdh in CK5‐positive cell lineages, and differential protein isoform expression, was additionally found in other tissues and cancer types, suggesting that overexpression of Phgdh is generally associated with CK5 cells, and that oncogenic function may be determined by isoform expression.     

Physiological effects of an additional stressor on fish exposed to a simulated heavy-metal-containing effluent from a sulfide ore smeltery

Perches (Perca fluviatilis), kept in slightly hypotonic brackish water, were exposed to dilutions of a simulated heavy-metal-containing effluent from a sulfide ore smeltery . Biochemical and hematological effects of the effluent, as well as the metal residues in liver and muscle tissues, were investigated after 12 and 27 days of exposure. The metal analyses revealed no significant uptake of metals in liver and muscle during the experiment. In spite of this, the exposed fish showed several physiological effects. Some of these, e.g., anemia, hypocalcemia, increased muscle water content, and reduced liver size, were of a transient nature, while others, such as disturbed chloride balance and hyperglycemia, seemed to be more persistent. At the end of the experiment (29-33 days of exposure), the physiological response to stress treatment (asphyxia) and a subsequent recovery were studied in exposed and unexposed fish. This stress investigation indicates that an additional stressor may strengthen the toxic effects of the heavy-metal-containing effluent. Furthermore, the secondary stress responses were more pronounced and the ability to recover from them seemed to be impaired in exposed fish as compared to unexposed fish.     

Sublethal physiological effects of chlorinated paraffins on the flounder, Platichthys flesus L.

Exposure of flounder, Platichthys flesus L., to two different chlorinated paraffin preparations, Witachlor 149 and Hülz 70C, caused sublethal effects on hematology and intermediary metabolism, together with changed activities in xenobiotic and steroid metabolizing enzymes, especially in female fish. The changes observed must be considered important and urge for further studies as the chlorinated paraffins are used in steadily increasing amounts and constitute a possible ecological threat.