Ageing and compositional changes of rat lens

In order to elucidate chemical changes in the lenses of aged animals, carbohydrate and fatty acid compositions were studied in 36 healthy male and female Fischer 344 rats from 3 weeks to 32 months of age. Senile cataract was observed on six lenses of 12 rats aged 28–32 months.The carbohydrate content increased rapidly within 7 months of age and remained constant until 29 months. But the myoinositol content showed a maximum at 7 months of age and aftewards a decreasing trend was observed. In cataractous lenses, the myoinositol content decreased rapidly; sorbitol and fructose showed similar changes although the rates were much lower than that of myoinositol.Lens fatty acids increased steadily during the life span and the ratio of unsaturated to saturated fatty acids was maintained in a narrow range (1.20–1.30). However, the value was significantly altered in cataractous lenses. An age-dependent change was found with nervonic acid, which increased markedly from 1.8% of fatty acids at 3 weeks of age to 6.8% at 29 months. In cataractous lenses, the predominant changes noticed were a rapid decrease of arachidonic acid and a high content of nervonic acid.     

Metabolic disorders of the liver

Metabolic diseases could be inherited as inborn errors of metabolism or acquired. In this review we discuss some of the metabolic disorders likely to present in the adult population and in which liver biopsy could be indicated as part of diagnosis or treatment. These include iron overload/hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, Niemann–Pick's disease and Gaucher's disease with emphasis on characteristic or helpful histopathologic features. In this era of molecular and other non-invasive analyses, the role of liver biopsy for primary diagnosis has decreased but is still an important tool for supplementing clinical/molecular diagnosis, staging disease and as a guide to management. In addition to qualitative assessment, quantitative measurements of iron and copper per unit dry weight of liver tissue can be performed on paraffin-embedded blocks and should be considered in patients being treated for iron overload or being worked up for possible Wilson's disease respectively. Gaucher's disease and Niemann–Pick's disease are examples of lysosomal storage diseases that could present outside of the pediatric population; these diseases have fairly distinguishing features that could be used to triage which patients need additional enzyme or other assays for definitive diagnoses. While non-alcoholic steatohepatitis remains the commonest metabolic liver disease in adult population, the pathologist should also be aware of these other entities discussed in this review.     

Clinical significance of triglyceride-rich lipoproteins in metabolic syndrome

Increase in triglyceride (TG) -rich lipoproteins is one of the symptoms clustered in metabolic syndrome and is associated with increased plasma free fatty acid level derived from central obesity and insulin resistance. Increase in triglyceride (TG) -rich lipoproteins is also related to several coronary risk factors such as remnant hyperlipidemia, decreased HDL-cholesterol, elevated small dense LDL, postprandial hyperlipidemia, and hypercoagulability. The first line of treatment for hypertriglyceridemia is the modification of individual life-style, among which, restriction of over-eating and practice of regular exercise are both essential. The consideration of dietary composition, not only the quantity but also the quality of nutrients, such as fat and carbohydrate, and behavior toward diet are also important to manage abnormal lipid profile. Statins, fibrates, nicotinic acid derivatives, and EPA are the drugs recommended for the treatment of dyslipidemias in metabolic syndrome.     

Age changes in hepatic metabolic characteristics and their modulation by dietary manipulation

Enlargement of the popliteal lymph node (PLN) of 6-week-old mice were elicited by the footpad injection of spleen cells of sex-matched, syngeneic, older mice, but not of 6-week-old mice, in a fashion of host-vs.-graft reaction. Effective stimulating cells in the inoculum seem to be Ia-bearing adherent cells. On the other hand, neither B and T cells nor immunoglobulin-secreting cells were effective for host T cell stimulation. Among nonlymphocytic adherent cells, only those attached to plastic dishes after a 24 h-incubation, enriched in macrophages, showed the stimulatory activity for the young recipients, while cells which had adhered once but detached and became non-adherent during a 24 h-incubation or a crude non-macrophage fraction did not induce the PLN response. Thus, the age-related antigenic change may occur on macrophages but not on dendritic cells. The effective cells should be alive, heat-killed cells being impotent to elicite the response. Such spleen adherent cells of aged mice were found to be also stimulative for age-matched recipients, when they are older than 3 months. Autostimulation by macrophages might be responsible, at least in part, for the age-related change of immune functions.     

Temperature-dependent compositional changes in the envelope of phi 6.

Bacteriophage φ6 contains lipid in an envelope that covers an icosahedral core. The envelope has six proteins, of which two constitute the attachment apparatus. The latter are designated P3, the host attachment protein, and P6, its anchor in the phage envelope. The number of molecules of P3 and P6 seem to be equivalent in the particle, but the relative amounts of the two proteins compared to other phage proteins vary with temperature. In phage grown above 24° there is about one-fourth as much P3 and P6 in the particles compared to phage grown below 24°. A result of this compositional change is a reduction in the rate of sedimentation of the virus formed at high temperature. A nonsense mutant defective in the synthesis of protein P6, which makes particles that contain lipid and other membrane proteins but lack P3 and P6 in the envelope, sediments at the same rate as wild-type virus grown at high temperatures. The sedimentation rate of such P3, P6-deficient particles is independent of the temperature at which they are formed. The variation in the amount of P3 and P6 inserted into the phage membrane reflects an aspect of assembly other than synthesis, since the relative amount of the two proteins synthesized with respect to other phage proteins does not change much with temperature.     

Possible genetic link between eating disorders and seasonal changes in mood and behavior.

Studies suggest that there is a seasonal pattern of mood fluctuations and eating behavior in patients with eating disorders. Multiple lines of evidence suggest that serotonergic pathways are involved in the mechanisms of eating disorders and seasonal changes in mood and behavior. Researchers have investigated whether variants of genes related to serotonergic transmission are associated with seasonal affective disorder (SAD) and eating disorders. There is evidence that the -1438G/A promoter polymorphism of the 5-HT2A gene plays a role in the development of SAD and eating disorders. Variation of the tryptophan hydroxylase gene may play a part in eating behavior and weight regulation in females with SAD. The author suggests that there may be a genetic link between SAD and eating disorders. It is possible that there are specific inherited personality types with a predisposition to both eating disorders and SAD.     

Intra-amygdaloid injections of kainic acid: regional metabolic changes and their relation to the pathological alterations

Kainic acid was injected unilaterally in the amygdala of the rat. Following various delays, 2-deoxy-D-[14C]glucose was given intravenously. Autoradiographs of frontal brain sections showed increased glucose uptake in a number of cerebral structures as compared with controls. Most of these structures belong to, or are closely related to, what is traditionally called the 'limbic system'. The structures that show an increased glucose consumption subsequent to kainic acid injections are, with few exceptions, identical to those that are sensitive to the toxic effect that kainic acid exerts on structures distant to the site of injection. The findings are discussed in relation to the hypothesis that the latter effect is secondary to the epileptogenic properties of kainic acid.     

Rickettsial Hemolysis: Effect of Metabolic Inhibitors upon Hemolysis and Adsorption

The hemolysis of sheep red blood cells by typhus rickettsiae is initiated by a temperature-sensitive adsorption process that is dependent on the energy-generating metabolism of the rickettsaie but not that of the erythrocyte. Adsorption is followed by events dependent on the metabolism of both the rickettsaie and red blood cells. At 34 C the adsorption step is complete after about 4 min, at lower temperatures the time required for adsorption is increased. At 0 C no adsorption occurred. The addition of cyanide inhibited the catabolism of glutamate by the rickettsiae and, consequently, both adsorption and the subsequent steps in hemolysis. The starvation of the rickettsiae for glutamate also prevented adsorption. Fluoride had no demonstrable effect on rickettsial metabolism nor the adsorption step but inhibited glycolysis in the erythrocytes and the hemolysis of the erythrocytes by rickettsiae.     

Metabolic and molecular basis of peroxisomal disorders: a review

The group of peroxisomal disorders now includes 17 different disorders with Zellweger syndrome as prototype. Thanks to the explosion of new information about the functions and biogenesis of peroxisomes, the metabolic and molecular basis of most of the peroxisomal disorders has been resolved. A review of peroxisomal disorders is provided in this paper.     

Reproductive decisions of parents of children with metabolic disorders

The Interaction Model of Client Health Behavior (IMCHB) served as a guide for variable selection and instrument development for telephone interviews with 230 parents of children with metabolic disorders. Sociodemographic, psycho-affective and client-professional interaction variables were examined in relation to three outcomes: (1) receptivity to future prenatal diagnosis (56% were receptive); (2) likelihood of terminating an affected pregnancy (10% would); and (3) whether or not the parent had taken measures to prevent another affected pregnancy (41% had). All three outcomes were significantly correlated with higher scores on the Parent Stress Index, lower scores on the Vineland Adaptive Behavior Scales, fewer persons in the parent's social support network, greater worry about the living child's future and greater perceived difficulty meeting the child's extra care needs. A regression model constructed to explain taking measures to prevent a future affected pregnancy illustrated the usefulness of the IMCHB in research that involves multiple interacting variables on health outcomes. Few of the parents (7.4%) reported an interaction with a genetic counsellor, highlighting the need for practitioners from multiple disciplines to be adequately educated in principles of genetics, especially the psychological and affective aspects of counselling.