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Fabry disease (FD) is an X-linked rare disorder caused by mutations in the GLA gene. Women with FD have been less enrolled in studies and less treated compared with men. The aim of the present study is to describe the complete phenotype of the women cohort with FD diagnosed and evaluated in Romania and compare it to the male population. This study included all consecutive patients diagnosed with FD referred to the Expert Center for Rare Genetic Cardiovascular Diseases between 2014-2023 which included 73 consecutive Romanian FD patients: 41 women (56.2%) and 32 men (43.8%) from 33 unrelated families. Women with FD were diagnosed later and had a later symptom onset. Comparing with men, women were less often symptomatic, but with similar symptom severity. They had similar ophthalmologic and ENT involvement, but less angiokeratomas. Both women and men had similar heart failure symptoms, which were usually mild to moderate, with no difference between the age of developing of the heart failure symptoms. There were also similar rates of acroparesthesia and stroke between sexes, but women presented less renal involvement, with less requirement for renal transplant. This study demonstrates that women with Fabry disease are not just carriers of the disease, they can present symptoms as severe as men, and they have less or later access to pathogenic therapy. Further studies with more female participations are needed to better understand the burden of Fabry disease in women., (© 2024 Adriana Mursă et al., published by Sciendo.)

In this paper, we present a three-dimensional mathematical model for a normal hip joint. The three-dimensional finite element model has been constructed based on Computer Tomograph scans of the bones. The obtained 3D model is studied using the finite element method, taking into consideration the real structure of the bone and the mechanical characteristics of cortical and spongy. The FE model of hip joint, the material properties used to simulate the behavior of the cortical and trabecular bone (of femur and coxal bone) and the cartilage, as well as the boundary conditions are presented. The distribution map of the axial and global movements on the global model and the distribution map of the axial and von Misses strain in the cartilaginous surface of the femur are presented.

In the past decades, chronic kidney disease has become a public health problem all over the world. Both the incidence and the prevalence are continually increasing. Diabetic nephropathy is, by far, the most frequent cause of CKD, with a prevalence of 40% in patients with end-stage renal disease (ESRD). Present studies have shown the fact that microalbuminuria and chronic kidney disease are independently associated to a high risk of cardiovascular events, as well as to a high mortality rate of all causes and also of cardiovascular cause, both in the general population and also in patients with high risk or an already present cardiovascular disease. There is a permanent association between the level of urinary albumin excretion and the risk for cardiovascular disease, macroalbuminuria and clinical nephropathy being associated to a higher risk for cardiovascular events than microalbuminuria. Due to the importance of clinical data and low cost, microalbuminuria and glomerular filtration rate should be introduced in the clinical practice for the evaluation of cardiovascular risk, especially in the patients with previously known heart disease. An early identification of the factors that determine the emergence and progression of diabetes complications is essential, in order to reduce the cardiovascular mortality and morbidity.

Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, generates abnormal thyroid--immune interactions, implicating an array of cytokines and their receptors. Thyrocytes achieve antigen presenting cell properties which stimulate effector immune cells (Th1, Th2, Th17), in the context of defective immunomodulatory T regulatory cells, resulting in thyroid lymphocytic infiltration and activation of B cells, with production of antibodies against thyroid antigens, thyroid destruction or stimulation, depending on the Th1-Th2 balance. During pregnancy there is a Th2 predominance sustained by the increased glucocorticoid, estrogen and progesteron levels, which allows tolerance versus the histoincompatible fetoplacental unit. In the postpartum period, the return shift Th2 to Th1 favors the occurrence of postpartum thyroiditis. Altered thyroid hormone levels can influence the immune system, and, on the other side, some immune cells secrete TSH, which exerts endocrine and paracrine, cytokine-like effects. Understanding the complex pathogenesis of autoimmune thyroid disorders is crucial for prevention and management.

Diabetic nephropathy (DN) is the result of numerous risk factors, such as hyperglycaemia, several genetic polymorphisms, offering susceptibility or individual resistance to DN. There are numerous, well-studied risk factors for DN, the majority being renal extrinsic, but there have been identified and studied renal intrinsic factors (the number of glomeruli, the volume of glomeruli) which can be structural determinants of the risk for the development of DN and may be precocious markers of DN. The clarification of the role of genetic factors in the pathogeny of DN may contribute to the evaluation of DN risk, allowing the selection of patients eligible to new precocious therapies (primary prevention) and the prevention of ESRD (secondary prevention).

Chronic hepatitis C and obesity inflict significant health and economic burdens on the world. Insulin resistance associated to obesity is the key factor in this disease, mainly because it has been related to fibrosis extension and non-response to antiviral therapy. The mechanism underlying this correlation is not fully explained yet. Leptin, adiponectin, TNF alfa, the hepatic expression of suppressor of cytokine signalling 3 (SOCS3), and hyperinsulinemia have been considered as heavily influencing fibrosis extension and nonresponsiveness to the IFN-alpha. The adipokines increased hepatic expression of SOCS3, and hyperinsulinemia has been proposed as heavily influencing non-responsiveness to the IFN-alpha and fibrosis extension by maintaining the hepatic stellate cells activated phenotype in patients with chronic hepatitis C and insulin resistance-related obesity. We shall review the mechanisms by which obesity-related insulin resistance may be associated with fibrosis extension and decreased efficacy of IFN-alpha based therapies in obese individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies. Consequently, being aware of the role of obesity-related insulin resistance in chronic hepatitis C, it will be possible to elaborate new therapeutic strategies for chronic hepatitis C obese patients. Also, it will be possible to elaborate new criteria for the initiation of antiviral therapy by including parameters such as body weight, abdominal circumference, HOMA-IR, the dosage of adipokines in order to more accurately define the groups of patients with a higher risk of non-responsiveness to antiviral therapy, thus lowering long-term costs.

Soya, cultivated for more than 3000 years, is both a drug and a food product. It has numerous nutritional benefits, given by its content of isoflavones, essential amino acids, fibers, poly-unsaturated fatty acids, vitamins and minerals. The use of soy reduces the risk of cardiovascular diseases: it has an antioxidant effect, reduces cholesterol levels and modulates the endothelial function; the soy foods, rich in isoflavones, reduce the risk of breast cancer; men with heredocolateral cancer antecedents or with minimal increase of prostate antigen must consider the consumption of soy and soy foods. Soy and soy foods play an important role in reducing the incidence of osteoporosis and controlling the pre- and postmenopausal symptoms; the soy ingestion has benefic metabolic effects in patients with Diabetes Mellitus and overweight. Taking into consideration the nutritional profile of soy, the nutritionists should encourage the population to consume more soy and soy foods. Nevertheless, long term studies are needed to discover a possible "dark side" of soy consumption. Among the most popular soy foods we mention: soymilk, soy cheese (tofu), soy meat (pie, salami, textured soy in granule form). Most of the products are soy flour derivatives, while tofu is obtained by curdling soymilk.

Turner syndrome (TS) is characterized by an increased prevalence of hypothyroidism, the main etiology being autoimmunity. The aim of our study was to assess the prevalence of hypothyroidism in patients with Turner syndrome, to analyze the correlations with clinical, chromosomal, hormonal and metabolic features and to compare hypothyroid with euthyroid Turner subjects. We studied 28 patients with TS (mean age 24.68 +/- 9.59yr). 78.57% with 45,XO. 10.71% with 45,XO/46,XX and 10.71% with other karyotypes. Hypothyroidism was diagnosed in 10 patients (35.7%). TSH level was positively correlated with thyroid autoantibodies titer (p < 0.001), maternal age at conception (p< 0.01), the presence of spontaneous puberty (p < 0.05) and relative height (p < 0.05), and negatively correlated with FSH level (p < 0.001) which is an indicator of the estrogenic status, and was not correlated to karyotype. Hypothyroid Turner subjects had higher relative heights (p < 0.05) and lower FSH levels (p < 0.05) than euthyroid subjects, but cholesterol levels and BMI were not significantly different.

Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner subjects as compared to normal females, and tends to develop at a younger age, but it is usually mild and responsive to weight loss or monotherapy. The primary pathogenic event is beta cell dysfunction, but insulin resistance also plays a central role and is worsened by the presence of hypertension, obesity and dyslipidemia which are common in Turner syndrome. We present the case of a 30 year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg, waist circumference 79cm, triangular facies, downslanting palpebral fissures, low set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria, polydypsia of three months duration and a fasting morning glucose of 260 mg/dL. Cardiac and renal defects were excluded, hormonologic evaluation was consistent with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51 U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet only; therapy consisted of hormone replacement theraphy, thyroxine and beta blockers.

Klinefelter syndrome is a hypergonadotropic hypogonadism determined by the presence of one or more extra X chromosomes and has an incidence of 1:800 males. It was shown that in Klinefelter syndrome mortality is increased due to diabetes, cardiovascular, respiratory and digestive diseases. Our goal was to assess the presence of metabolic changes which can increase cardiovascular risk. We compared 31 untreated Klinefelter patients aged 19-54 years (mean age 33.84 years, SD 11.79 years) with 31 age matched controls. Hypercholesterolemia was present in 56.67% of Klinefelter patients and correlated with age and the magnitude of androgenic deficit. None of the patients had diabetes mellitus but glycemic values above 100 mg% were present in 16.13% of cases (vs 3.2% in controls). 35.5% of Klinefelter patients and controls were overweight and 16.1% of Klinefelter patients were obese vs 9.7% of controls.

The authors studied the cerebral irrigation on a group of 18 patients with Alzheimer disease (60-70 year old) using the Doppler (D) ultrasound vascular method and EEG. They used a type UDP-10 Sonopan, with a sound acquisition system and graphic of recording on a 6 NEK-4 polyrecorder for registration of the carotid D curves together with ECG and phonocardiogram. EEG was registered using a Bioscript 2000. The statistical analysis of the D curves parameters for a group of 18 patients, compared to the parameters of a group of 40 clinically healthy persons, showed a decrease of the systolic speed with 24% and of the diastolic speed with 11%, a delay of the flow with the systolic spike in plateau and a murmur at the carotid arteries in 33% of the patients. These modifications point to the reduction of the cerebral vascular filling, determined especially by the atherosclerosis process which causes important narrowing of the vascular lumen but probably determined by Alzheimer disease also. We remarked the presence of theta waves in 42% of the patients and a small correlation (r = 0.38) with the decrease of the systolic speed in the test group.

The vascular chronic complications are the main cause of morbidity and mortality in patients with diabetes mellitus. Nowadays it is well known the fact that the arteriosclerosis is initiated by the injury of the vascular endothelium and that the normal endothelial cells are producing a number of vasoactive factors. Thus, the vascular endothelium was considered an inert "lining" layer, but today is seen as a complex organ, with paracrin and autocrin function, which provides a "first line" physiological defence against atherosclerosis. Impaired endothelial function occurs in people with diabetes as a result of associated conditions (e.g. hyperglycemia, hypertension, dyslipidemia), or as an effect of hyperglycemia itself (e.g. cytokines, free fatty acids, AGES). The presence of endothelial dysfunction in non diabetic insulin resistant subjects suggests that metabolic and vascular abnormalities are tightly related at a fundamental level. Recent evidence suggests that insulin signalling for glucose transport in classical target tissues (muscle and adipose tissue) and upregulation of NO production in the endothelium utilises the same postreceptor pathway. This pathway involves the enzyme P13 kinase. Knowledge of the molecular mechanisms involved in the pathogenesis of endothelial dysfunction may ultimately result in novel approaches to the treatment and prevention of cardiovascular disease in people with diabetes mellitus.

Our study concentrated upon the modifications of some parameters which characterize uterine smooth muscle contractile activity under the action of active substances. We studied the isotonic contractions of the uterine smooth muscle in a classical organ bath in which we introduced some contracting and relaxing substances. At the beginning, we introduced Oxytocin to determine uterine smooth muscle contractions. After that, we added relaxing substances (Papaverin, Diazepam, Terbutalin, Isoxuprin, Hexoprenalin) in the organ bath, and then, in another protocol, we added combinations of two relaxing substances. We determined for each wave some parameters: minimum, mean, maximum and net amplitude, wave area and duration, the interval between waves, the time while the curve increases from the minimal value of the amplitude to the maximum value, the frequency of contractile waves. For each parameter we determined the variance coefficient (C.V. %), which reflects the regularity of the uterine activity. We observed a regularizing effect of the uterine activity after administration of some active substances. The smallest variance coefficient (C.V. %) was found for HEXO + PAP combination (mean value for C.V. % is 4.71%).