β-Thalassemia Haplotypes in Romania in the Context of Genetic Mixing in the Mediterranean Area

The purpose of this meta-study was to investigate β-thalassemia (β-thal) mutations and their chromosomal background in order to highlight the origin and spread of thalassemia alleles in the European and Mediterranean areas. Screening of more than 100 new Romanian β-thal alleles was also conducted. The results suggest an ancient introduction of mutations at codon 39 (C?>?T) (HBB: c.118C?>?T) and IVS-I-6 (T?>?C) (HBB: c.92?+?6T?>?C) in Romania. A comparative study was performed based on restriction fragment length polymorphism (RFLP) haplotypes associated with β-thal mutations in Romania and in Mediterranean countries. Each common β-thal allele from different populations exhibits a high degree of haplotype similarity, a sign of a clear unicentric origin for the IVS-I-110 (G?>?A) (HBB: c.93-21G?>?A), IVS-I-6, IVS-II-745 (C?>?G) (HBB: c.316-106C?>?G) and codon 39 mutations (the 17a [+?????????+?+], 13c [???+?+???????+], 17c [?+???????????+] and 14a [??+?+???+?+?+?] ancestral RFLP background, respectively), followed by recurrent recombination events. This study also showed that geographic distances played a major role in shaping the spread of the predominant β-thal alleles, whereas no genetic boundaries were detected between broad groups of populations living in the Middle East, Europe and North Africa. The analyses revealed some discrepancies concerning Morocco and Serbia, which suggest some peculiar genetic flows. Marked variations in β^A were observed between Southeast Asia and the Mediterranean, whereas a relative genetic homogeneity was found around the Mediterranean Basin. This homogeneity is undoubtedly the result of the high level of specific historic human migrations that occurred in this area.     

Does the presence of diabetic nephropathy in parents influence the metabolic response in the offspring?

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) and long-term complications such as nephropathy have a strong genetic predisposition. Insulin resistance is thought to be a pathogenetic factor, predisposing genetically prone individuals to develop the microvascular complications of diabetes. To test these hypotheses, two groups of young individuals were studied: 28 offspring of parents having NIDDM and diabetic nephropathy (group 1) aged 29.5 ± 6.1 years, BMI 25.2 ± 4.7 kg m⁻² and 31 offspring of diabetic parents with no history of nephropathy, aged 31.6 ± 4.1 years and BMI 26.3 ± 4.9 kg m⁻² (group 2). All underwent a standard oral glucose tolerance test with measurement of serum insulin levels and serum lipid profile. Urine albumin:creatinine ratio (A/C ratio) and blood pressure were also recorded. Diabetes was detected in 2/28 (7.1 %) and 3/31 (9.7 %) and IGT was detected in 5/28 (25 %) and 8/31 (25 %) of groups 1 and 2, respectively. These differences were not statistically significant, but were higher than in a group of non-diabetic controls with healthy parents. Comparison of the normoglycaemic subjects (19 and 20 in group 1 and 2, respectively) showed no significant differences between blood pressure readings, fasting and 2 h plasma glucose, and lipid profiles. Plasma insulin values, fasting and 2 h, and the area under the graph were also similar in both groups, indicating an absence of higher insulin response in group 1 in comparison with group 2. These values were also not different from those in the non-diabetic controls. A delay in insulin response to glucose was noted in many of the offspring as indicated by a low ΔI/ΔG at 30′. We conclude that offspring of diabetic parents with nephropathy do not show higher risk of glucose intolerance or insulin resistance compared to those with diabetic parents without nephropathy. The relatively high plasma glucose values in the presence of normal insulin secretion in both groups of offspring of diabetic parents suggest the presence of insulin resistance. © 1997 John Wiley & Sons, Ltd.     

Gastro-entero-hepatology in the New Millennium

The global prospects for gastroenterology are excellent. The subspecialty involves the largest area of body surface, the largest endocrine organ, the largest neuronal organ (with 200 million neurones), and the largest immune organ (with 50 % of all lymphocytes); it includes by far the largest number of diseases, many still unexplored, and the largest oncological patient load. Gastroenterology/hepatology lies at the cross-roads between internal medical and surgical specialties.     

Syncope-related falls in the elderly

Age-related physiological impairments of heart rate, blood pressure and cerebral blood flow, in combination with comorbid conditions and concurrent medications, account for an increased susceptibility to syncope in older adults. Common causes of syncope are orthostatic hypotension, neurally-mediated syncope (including carotid sinus syndrome) and cardiac arrhythmias. A high proportion of older patients with cardiovascular syncope present with falls and deny loss of consciousness. Patients who are cognitively normal and have unexplained falls should have a detailed cardiovascular assessment. (J Geriatr Cardiol 2005; 2 (2): 74-83).     

Endovascular interventions of the femoro-popliteal disease in the elderly

In the last few years the treatment of superficial femoral artery (SFA) occlusive disease has undergone greater changes in management including more aggressive endoluminal therapy, especially in the elderly patients who are at high risk for extra-vascular comorbidities from the surgical approach. While acute and chronic arterial limb ischemia is the conditions which the interventional cardiologists frequently encounter, the elderly population represents special problematic clinical and anatomical setting due to heavy calcification and poor distal run-off. Arterial thrombolysis, rheolytic thrombectomy, mechanical thrombectomy, laser angioplasty, cryoplasty, and new flexible long stents are some of the promising techniques to improve the technical and clinical outcomes in these elderly patients.     

Assessing the severity of the small inframe deletion mutation in the α-subunit of β-hexosaminidase A found in the Turkish population by reproducing it in the more stable β-subunit

GM(2) gangliosidoses are a group of panethnic lysosomal storage diseases in which GM(2) ganglioside accumulates in the lysosome due to a defect in one of three genes, two of which encode the alpha- or beta-subunits of beta- N -acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic domain of the alpha-subunit of Hex has been found in five Turkish patients with infantile Tay-Sachs disease. To date it has not been detected in other populations and is the only mutation to be found in exon 10. It results in detectable levels of inactive alpha-protein in its precursor form. Because the alpha- and beta-subunits share 60% sequence identity, the Hex A and Hex B genes are believed to have arisen from a common ancestral gene. Thus the subunits must share very similar three-dimensional structures with conserved functional domains. Hex B, the beta-subunit homodimer is more stable than the heterodimeric Hex A, and much more stable than Hex S, the alpha homodimer. Thus, mutations that completely destabilize the alpha-subunit can often be partially rescued if expressed in the aligned positions in the beta-subunit. To better understand the severity of the Turkish HEXA mutation, we reproduced the 12 bp deletion mutation (1267-1278) in the beta-subunit cDNA. Western blot analysis of permanently transfected CHO cells expressing the mutant detected only the pro-form of the beta-subunit coupled with a total lack of detectable Hex B activity. These data indicate that the deletion of the four amino acids severely affects the folding of even the more stable beta-subunit, causing its retention in the endoplasmic reticulum and ultimate degradation.