Effect of iron deficiency anemia on the development of atherosclerosis in chicks.

The effect of iron deficiency anemia on the development of atherosclerosis was investigated in chicks. The control group of birds were fed a basal diet, the atherosclerosis group received 1% cholesterol. The lipid content of the aortas of the chicks in atherosclerosis and atherosclerosis-anemia group also developed anemia of appreciable severity in 12 weeks. Hemoglobin and PCV were taken as the index of anemia, while the lipid constituents were determined in plasma and aortic tissue for atherosclerosis. Hypercholesterolemia of almost equal severity occurred in both atherosclerosis and atherosclerosis-anemia groups. The abnormal rise of cholesterol and other lipid material in the aortas of the atherosclerosis and atherosclerosis-anemia groups of birds indicates that iron deficiency anemia did not markedly affect the development of atheroslcerosis; it did not offer any protection in chickens and, in fact, a slight potentiating effect was observed.     

Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion

Diazoxide is a putative mitochondrial, ATP-sensitive potassium channel opener that has been implicated in neuroprotection in cerebral ischemia. Administered as pretreatment, diazoxide can attenuate ischemia-related neuronal injury, but little is known about the potential neuroprotective properties of the drug when it is given after the onset of an ischemic insult. In a previous study, we applied diazoxide after imposing chronic cerebral hypoperfusion by means of permanent, bilateral occlusion of the common carotid arteries (2VO) in rats. We observed that ischemia-induced learning impairment assessed in the Morris water maze, and microglial activation visualized by immunocytochemistry, were prevented by diazoxide as determined at 13 weeks after 2VO. However, dimethyl sulfoxide, the organic solvent of diazoxide also prevented memory deficits, without any effect on microglial activity. Therefore, we have repeated our experiments with the use of an inorganic solvent, aqueous NaOH solution in order to clarify the effect of diazoxide independent of dimethyl sulfoxide. The present results demonstrated that diazoxide alone did not improve learning performance, but it prevented microglial activation in the hippocampus 13 weeks after the onset of 2VO. These data provide evidence that post-treatment with diazoxide is not effective in impeding a long-term memory deficiency, but it can attenuate ischemia-induced microglial activation, independently of the solvent used.     

Frequency of loss of heterozygosity of the NF2 gene in schwannomas from Croatian patients

Aim. To identify gross deletions in the NF2 gene in a panel of schwannomas from Croatian patients in order to establish their frequencies in Croatian population. Methods. Changes of the NF2 gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using two microsatellite markers, D22S444 and D22S929. Results. The analysis with both markers demonstrated that 43.75% of schwannomas exhibited LOH of the NF2 gene. The D22S444 region exhibited 45.5% of LOHs and the D22S929 region exhibited 14.3% of LOHs. Four LOHs were found in Antoni B, 2 in Antoni A, and 1 in Antoni A and B type tumors. Conclusion. The frequency of changes observed in Croatian patients is broadly similar to that reported in other populations and thus confirms the existing hypothesis regarding the tumorigenesis of schwannomas and contributes to schwannoma genetic profile helping us to better understand its etiology and treatment.     

Heart in the elderly (views and considerations at the turn of the centuries)

The proportion of elderly people grows rapidly both in Croatia and worldwide, posing great health care, psychological, social, economic and other problems. In the elderly, cardiovascular diseases, especially coronary (ischemic) heart diseases, account for approximately 50% of all deaths. In contrast to previous opinions, recent studies show that aging per se does not substantially diminish the efficacy of heart pump unless affected by diseases, primarily atherosclerosis (atherothrombosis). Atherosclerosis, however, is not an inevitable component of old age, but a disease that can to a great extent be prevented, and hopefully even defeated in the near future. Of paramount importance is elimination of the major risk factors: cigarette smoking, hypertension, hyperlipidemia, diabetes mellitus, obesity, and physical inactivity, preferably in the form of primary prevention, primarily by the hygienic-dietetic measures, and by medication (antihypertensives, hypolipidemics), if necessary. The prevention should be initiated early enough to prevent the development of subclinical forms of the disease, because clinical manifestations (angina pectoris, myocardial infarction, serious ventricular arrhythmias, sudden death) occurring unexpectedly ('like a bolt from the blue') reflect a very advanced coronary disease. The management of these late complications, however admirable it may be (coronary dilatation--stents, coronary surgery, thrombolysis, resuscitation, electrotherapy, etc.), is only partially successful and in fact unavailable to the majority of the population, even in developed countries. Therefore, every individual should be informed about the main characteristics of the issue to be able to take active participation in the programs of primary prevention. Although the relative importance of particular risk factors decreases in old age, these factors are present in a higher number in the elderly which, along with the generally greater mortality rate, points to the need of all measures (primary and secondary) of prevention to be as carefully carried out in the elderly as in younger individuals.     

Sexual dimorphism of the extraorbital lacrimal glands in SF-1 knockout mice

Sexual dimorphism (SD) represents all the differences between males and females of the same species. SD of the murine lacrimal gland and the major effect of testosterone on its formation are well documented. Steroidogenic factor-1 (SF-1, NR5a1) is a nuclear receptor essential for the fetal development of steroid hormones producing organs and SF-1 knockout mice (Sf-1 KO) are therefore born without gonads and adrenal glands. The aim of this study was to investigate whether SD in lacrimal glands is present in the absence of exposure to sex hormones during development. Lacrimal glands from adult Sf-1 KO male and female mice without hormonal exposure, and from males that were treated with testosterone propionate (TP) prior to sacrifice, were examined. After sacrifice, glandular tissue was processed using standard histological procedures. Paraffin sections were analysed by stereology and immunostained against the androgen receptor (AR). Our results showed that there were no statistically significant differences in the mean volumes of acini, connective tissue or ductal system between males, females, and males on TP. The same pertains to the mean length of the ducts in all three groups. In the absence of sex hormones, sex chromosomes proved to be insufficient in inducing sexual dimorphism in LG. However, nuclei of the acinar cells in males on TP were positive for AR, whereas in males without TP no expression of AR was detected. Administration of TP induced the expression of AR in the nuclei of acinar cells of males but did not affect the morphology of LG. We conclude that SD in the lacrimal gland is not present in Sf-1 KO mice and this suggests that sex hormones have a major role in the development of SD in the lacrimal gland.     

Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A

Classical Hutchinson-Gilford progeria syndrome (HGPS) is caused by LMNA mutations that generate an alternatively spliced form of lamin A, termed progerin. HGPS patients present in early childhood with atherosclerosis and striking features of accelerated aging. We report on two pedigrees of adult-onset coronary artery disease with progeroid features, who were referred to our International Registry of Werner Syndrome (WS) because of clinical features consistent with the diagnosis. No mutations were identified in the WRN gene that is responsible for WS, among these patients. Instead, we found two novel heterozygous mutations at the junction of exon 10 and intron 11 of the LMNA gene. These mutations resulted in the production of progerin at a level substantially lower than that of HGPS. Our findings indicate that LMNA mutations may result in coronary artery disease presenting in the fourth to sixth decades along with short stature and a progeroid appearance resembling WS. The absence of early-onset cataracts in this setting should suggest the diagnosis of progeroid laminopathy. This study illustrates the evolving genotype-phenotype relationship between the amount of progerin produced and the age of onset among the spectrum of restrictive dermopathy, HGPS, and atypical forms of WS.     

Screening for fragile X syndrome: results from a school for mentally retarded children

Fragile X syndrome is the most common inherited form of familial mental retardation. The purpose of this study was to identify yet unrecognized fragile X individuals and to estimate the frequency of both the FRAXA and FRAXE forms of the disease in a population of mentally retarded children attending a special school in Croatia. The results are reported of molecular screening of 114 children with mild to severe mental retardation. Three individuals (2.6%) with the FRAXA form of the fragile X syndrome and one boy (0.9%) with FRAXE mental retardation were detected; a total of four newly diagnosed fragile X families were identified. Closer clinical examination revealed that behavioural and speech disturbances were clearly present among all fragile X cases (both FRAXA and FRAXE), indicating that these features could be additional diagnostic criteria for the preselection of individuals at risk.

Conclusion: Fragile X screening among mentally retarded children attending a special school should be highly encouraged to reveal the cause of mental retardation and to detect yet unrecognized fragile X individuals. The frequency of fragile X syndrome in a such population in Croatia was found to correlate with similar results from previous studies. However, since at the time of diagnosis all affected families had a second or even a third child born, earlier diagnosis should be considered to provide greater benefit to fragile X families.     

Martin-Gruber anastomosis revisited

Based on a study of 70 human cadavers (31 male, 39 female) and on cases described previously, we propose a new classification of the Martin-Gruber anastomosis, a neural connection between the median and ulnar nerves in the forearm. The anastomosis was found in 16 (22.9%) cadavers, being bilateral in three (18.7%) and unilateral in 13 (81.3%), five right and eight left. It occurred in eight (25.8%) of the 31 male cadavers and in eight (20.5%) of the 39 females. Therefore, the anastomosis was found in 19 (13.6%) of the 140 forearms. In Pattern I (89.5%) the anastomosis was made by only one branch, whereas in Pattern II (10.5%) it was made by two. The individual branches were classified as Types a, b, and c based on the nature of their origin from the median nerve. Type a (47.3%) arose from the branch to the superficial forearm flexor muscles, Type b (10.6%) from the common trunk, and Type c (31.6%) from the anterior interosseous nerve. Pattern II was a duplication of Type c (10.5%). The anastomotic branch took an oblique or arched course before joining the ulnar nerve, undivided in 15 cases, but divided into two branches in four cases. The anastomosis passed in front of the ulnar artery in four cases, behind it in six, and in nine cases it was related to the anterior ulnar recurrent artery.