Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance.

AIMS: Obesity is associated with insulin resistance, liver steatosis and low-grade inflammation. The role of oestrogen in sex differences in the above co-morbidities is not fully understood. Our aim was to assess the role oestrogen has in modulating adipocyte size, adipose tissue oxidative stress, inflammation, insulin resistance and liver steatosis. METHODS: To determine the role oestrogen has in the above co-morbidities related to obesity, we randomized C57BL/6J mice into four groups (15 mice per group): (i) male, (ii) non-ovariectomized female (novx), (iii) ovariectomized female (ovx) and (iv) ovariectomized female mice supplemented with 17ß estradiol (ovx-E). Mice received either a low-fat (LF) or a high-fat (HF) diet for 10 weeks. Outcomes measured were bodyweight, body fat, adipocyte diameter, adipose tissue lipolysis markers, adipose tissue oxidative stress, inflammation, insulin resistance and liver steatosis. RESULTS: Male and ovx-female mice consuming the HF diet had a higher propensity of gaining weight, specifically in the form of body fat. Oestrogen protected female mice from adipocyte hypertrophy and from developing adipose tissue oxidative stress and inflammation. Moreover, novx-female and ovx-female+E mice had higher phosphorylated levels of protein kinase A and hormone sensitive lipase, markers associated with lipolysis. Additionally, male and ovx female mice had a higher propensity of developing liver steatosis and insulin resistance. In contrast, oestrogen protected female mice from developing liver steatosis and from becoming insulin resistant. CONCLUSION: We show that oestrogen protects female mice from adipocyte hypertrophy and adipose tissue oxidative stress and inflammation. Furthermore, oestrogen prevented female mice from developing liver steatosis and from becoming insulin resistant.

[Predictive value of aortic atherosclerosis detected by transoesophageal echocardiography for the presumption of coronary artery disease]. / Valeur prédictive de l'athérosclérose aortique détectée par l'échocardiographie transoesophagienne dans la présomption de l'athérosclérose coronaire.

The aim of this study was to determine the relationship between plaques of aortic atheroma detected by transoesophageal echocardiography and the condition of the coronary arteries at coronary angiography. Two hundred and seventeen consecutive patients were included for systematic transoesophageal echocardiography blinded to the results of coronary angiography. Significant coronary disease was defined as stenosis of at least 70% of the artery lumen. Aortic atherosclerosis was classified in four grades. The average age of the patients was 54.5 +/- 10.5 years. The sex ratio was 2.55 in favour of men. The average coronary score was 5 +/- 4.5 and the lesion index was 1.1 +/- 0.96. One hundred and fifty-nine patients had aortic atheroma, 73% of which (80 cases) were complex lesions. The descending aorta was the commonest site (91%) followed by the transverse (40% and ascending aorta (14%). When the ascending aorta was affected there was a very significant association with coronary artery disease (100% of cases). Sixty-one per cent of patients had lesions of one aortic segment, 28% had lesions of two aortic segments and in 10%, all three aortic segments were involved. The presence of aortic atheroma was correlated with coronary artery disease with a sensitivity and specificity of 86% and 76% respectively. The positive and negative predictive values were 81% and 31% respectively. Seventy-five per cent of patients with a coronary score of at least 7 had aortic atheroma with complex lesions in 47% of cases. The lesion index was significantly higher in this group when the coronary score was less than 7 (1.98 +/- 0.8 vs 0.65 +/- 0.7, p<0.00001). Patients with coronary artery disease have more complex lesions of the descending than of the ascending aorta (94 vs 25%). Significant coronary artery disease was correlated with the presence of aortic atheroma, especially of the ascending aorta. The specificity and positive predictive values were 100% but the negative predictive value was poor, irrespective of the aortic segment involved (32% for the ascending aorta, 36% for the transverse and 35% for the descending aorta). The authors conclude that transoesophageal echocardiography of the thoracic aorta is a good method of predicting severe coronary atherosclerotic disease.

Cancer registration in the Middle East.

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.

Screening secondary school students in the Gaza strip for beta-thalassaemia trait.

A small scale screening study for beta-thalassaemia trait has been carried out in the Gaza Strip, involving 1650 secondary schools healthy students, 16-18 years old and from both sexes. The results showed that the overall prevalence in the Gaza Strip of beta-thalassaemia was 4.3%. The frequency of beta-thalassaemia trait in the microcytic (defined as MCV < or = 80fl and/or MCH < or = 26 pg) subjects was 27.1%. The efficacies of some of the proposed discrimination functions in the differentiation between beta-thalassaemia trait and non-thalassemic microcytosis were evaluated. The Mentzer index, MCV of < or = 72fl, England & Fraser DF and the Shine & Lal formula were found to correctly identify 91.6%, 82.4%, 81.3% and 62.6% of the studied cases of microcytosis as having or not having the beta-thalassaemia trait. It was concluded that both beta-thalassaemia and microcytic anaemias are major health problems in the Gaza Strip. The various forms of consanguineous marriages, in addition to poor economic conditions in the Gaza Strip may have contributed to the concentration of beta-thalassaemia and the prevalence of microcytic anaemias in this population.

Hepatitis C virus infection and genotypes in Southern Israel and the Gaza Strip.

The Gaza Strip borders the southern part of Israel and Egypt. There is a remarkable difference in the prevalence of antibodies to hepatitis C virus (HCV) between Israel (0.5%) and Egypt (10%). A few thousand inhabitants cross the borders daily from the Gaza Strip to both countries. The objectives of this study were to investigate the prevalence of HCV infection in the Gaza Strip, an area that was not studied before, and to study HCV transmission in the Gaza Strip by characterizing the genotypes of HCV in Southern Israel and the Gaza Strip and comparing them with those found in Egypt. HCV prevalence in the Gaza Strip was found to be 2.2%, relatively higher than in Israel but lower than in Egypt. The most common genotypes found were type 1 b in Southern Israel and type 4 in the Gaza Strip, corresponding to the most prevalent genotype in Egypt. Similarity between type 4 isolates from the Gaza Strip and Egypt was illustrated further by sequence analysis of the HCV 5' noncoding region (NCR).

Cancer patterns in the Middle East--special report from the Middle East Cancer Society.

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.

Two mutations in the beta-globin polyadenylylation signal reveal extended transcripts and new RNA polyadenylylation sites.

Two mutations in the beta-globin poly(A) signal were identified in Israeli patients with beta +-thalassemia by sequence analysis following PCR. One is a point mutation (AATAAA----AATAAG) and the other is a 5-base-pair deletion (AATAAA----A----). The mutant genes were used to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired. RNA obtained from the patients carrying the point mutation contained four discrete, extended RNA species, 1500-2900 nucleotides long, which were found to be polyadenylated. Some normal cleavage-polyadenylylation was also observed. The 5-base-pair deletion completely abolished cleavage at the normal site. This deletion mutation resulted in a phenotype of beta +-thalassemia, thus providing evidence that the extended mRNAs are translatable in vivo. Furthermore, additional transcripts, greater than 5 kilobases, presumably mRNA precursors, were found in all RNA samples, including those of nonthalassemic controls. The extended transcripts of the poly(A) mutants, together with the high molecular weight precursors, suggest that the human beta-globin gene transcription unit is significantly longer than previously recognized.

Results of treatment of high risk childhood acute lymphoblastic leukemia.

Sixteen children with high risk acute lymphoblastic leukemia (ALL) who had one or more of the following risk factors: white cell count over 50 X 10(9)/liter, mediastinal mass, age under 2 or over 10 years, extramedullary involvement, or T-cell markers, were treated by a new protocol. All attained complete remission and 11 are still in their continuous first remission for 6-53 months. High activity of adenosine deaminase (ADA) in the leukemic cells seems to be an independent risk factor, as in the high ADA level group, 4 out of 7 patients relapsed and died, while none of the 8 patients with low ADA levels relapsed or died.