Lactose Intolerance - Single Nucleotide Polymorphisms and Treatment.

The majority (about 70%) of the world's population suffers from lactose intolerance. Lactose intolerance leads to long-term discomfort when consuming milk and dairy products, and hence, to their avoidance. Consequently, the intake of important nutrients is reduced, which potentially has a negative impact on the overall health. Knowing the condition - lactose intolerance - will prevent people from unnecessarily restricting dairy products in their diets. In this study, lactose synthesis and catabolism in the human body are presented, also the types of lactose intolerance, as well as the methods of diagnosing this condition, are discussed. Special attention is paid to the genetic causes of this discomfort and to the tests that can be performed. Solutions for the treatment of lactose intolerance have also been proposed, both up-to-date and easily applicable, as well as future developments.

This review highlights the lactose pathway ­ from the mammary gland production to recipient gut hydrolysis.Lactose intolerance associated SNPs known so far are presented and discussed.Advice for people with lactose intolerance is presented in the form of possible treatments and healthy feeding behaviors.

Increased gene expression of TIMP1 and CHI3L1 in fine-needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules.

BACKGROUND: Thyroid nodules are common ultrasound findings with malignancy rate 7%-15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase-1 gene (TIMP1) and chitinase-3-like protein 1 gene (CHI3L1) in fine-needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP-1 and chitinase-3-like protein 1 known as YKL-40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated. METHODS: Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP-1 and YKL-40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR. RESULTS: The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p < .001 for TIMP1; p = .018 for CHI3L1). The PTC patients had higher serum TIMP-1 than the patients with benign nodules (p = .036). We did not find significant difference in the YKL-40 level between the two groups. TIMP1 and CHI3L1 expression did not correlate with the serum levels of their protein products. CONCLUSION: FNAB washouts could be used for identification of diagnostic markers. The increased TIMP1 and CHI3L1 expression implies a role of these genes in the PTC carcinogenesis.

Evaluation of the Diagnostic Performance of EU-TIRADS in Discriminating Benign from Malignant Thyroid Nodules: A Prospective Study in One Referral Center.

BACKGROUND: Several thyroid societies have endorsed ultrasound (US) malignancy risk stratification systems for thyroid nodules and the recently released European Thyroid Imaging Reporting and Data System (EU-TIRADS) needs large prospective studies for validation. OBJECTIVE: The purpose of our study was to evaluate the performance of EU-TIRADS in identifying thyroid nodules for fine-needle aspiration biopsy (FNAB) and its ability to reduce the number of unnecessary biopsies. METHODS: This was a single-center prospective study. From August 2017 to September 2018, 783 consecutive patients with 1,000 thyroid nodules underwent US examination and US-guided FNAB. A total of 741 patients (median age 50 years; range, 15-87 years; 649 females, 92 males) with 942 nodules (median largest diameter 14 mm; range, 4-96 mm) met the following inclusion criteria: (1) nodules with benign or malignant cytology - categories II and VI of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC); (2) nodules with non-diagnostic and indeterminate cytology (BSRTC I, BSRTC III, and BSRTC IV), or suspicious for malignancy (BSRTC V), if postoperative histology was present; (3) nodules classified as BSRTC I and BSRTC III with a repeat FNAB and conclusive cytology. RESULTS: Of 942 nodules, 839 (89.1%) were benign and 103 (10.9%) were malignant. Nodules were classified as follows: EU-TIRADS 2 - 4.8%, EU-TIRADS 3 - 37.4%, EU-TIRADS 4 - 25.2%, and EU-TIRADS 5 - 32.6%. The malignancy rate in categories 2 to 5 was 0, 0, 3.8, and 30.6%, respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EU-TIRADS with a cut-off set at category 5 were 91.3, 74.6, 30.6, 98.6, and 76.4%, respectively. Diagnostic performance other than sensitivity and NPV was superior in nodules ≥10 mm. FNAB number would be reduced by 53.4% if FNAB criteria were strictly applied. When the indication for FNAB was applied as test positivity, the estimated sensitivity, specificity, PPV, and NPV of EU-TIRADS were 69.9, 56.3, 16.4, and 93.8%, respectively. CONCLUSION: EU-TIRADS provides effective malignancy risk stratification that can guide the selection of thyroid nodules for biopsy. The application of the guidelines criteria for FNAB in the clinical practice might reduce significantly the number of unnecessary FNAB.

Thyroglossal duct cyst carcinoma.

Not required for Clinical Vignette.

Association of Serum Lipids with Hepatic Steatosis, Stage of Liver Fibrosis and Viral Load in Chronic Hepatitis C.

INTRODUCTION: Hepatitis C Virus (HCV) relies on host lipids for its life cycle contributing to lipid abnormalities and hepatic steatosis. Disease progression is influenced by viral factors interacting with host immune and metabolic pathways. The significance of serum lipids for Chronic Hepatitis C (CHC) assessment is not clearly established yet. AIM: Our aim was to investigate serum lipids' association with stage of liver fibrosis, steatosis and genotypes in patients with CHC. MATERIALS AND METHODS: A total of 112 CHC patients (54 male, 58 female, aged 48.6±13.7 years) were studied - 98 genotype 1 (G1) and 14 genotype 3 (G3). Liver cirrhosis (F4) was diagnosed in 31 cases. Steatosis was present in 75 of all patients on ultrasound. Liver biopsy was done in 65 patients and histology showed steatosis in 28, stages of fibrosis (F1-F3) in 56 and F4 in 9 patients (METAVIR). Laboratory panel included complete blood count, liver tests and serum lipid levels (mmol/l) with Friedewald equation estimations. Indirect noninvasive fibrosis scores FIB-4, Aspartate aminotransferase to Platelet Ratio Index (APRI) and Forns index were calculated. HCV RNA was quantified by RT-PCR. Statistical analysis included Spearman's rho, Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve. RESULTS: Total Cholesterol (TCh) (p=0.002) and Low-Density Lipoprotein (LDL) (p=0.003) in G1 patients were higher when steatosis was present. TCh (p<0.001), High-Density Lipoprotein (HDL) (p=0.018) and LDL (p=0.003) were lower in G1 F4 compared with F1-F3 patients. Triglyceride (TG) levels correlated with FIB-4 (r=0.364, p=0.029), APRI (r=0.333, p=0.047) and Forns index (r=0.423, p=0.010) in G1 patients without steatosis. TG to LDL ratio (TG/LDL) (p=0.001) was higher in F4 than in F1-F3 patients. TG/LDL ratio predicted the presence of F4 in G1 patients without steatosis by an area under the ROC curve 0.900 (p<0.001). TG/LDL ratio > 0.52 was highly specific for F4 without steatosis. Specificity dropped to 76% when steatosis was present. TG/LDL < 0.32 negatively predicted liver cirrhosis. HCV RNA correlated with TG levels (r=0.330, p=0.009) in G1 patients with steatosis and with histological percent of fatty hepatocytes (r=0.585, p=0.028) in G3 patients. CONCLUSION: Lipid levels in CHC G1 patients depend on the presence of steatosis and cirrhosis. HCV RNA is associated with TG levels in G1 patients with steatosis, but not in G3 patients. In cirrhotic CHC G1 patients cholesterol is low with relatively increased TG. TG/LDL ratio is a potential marker of liver cirrhosis in CHC G1 patients.

Evaluation of prognostic utility of MIB-1 and p53 expression in pituitary adenomas: correlations with clinical behaviour and follow-up results.

Pituitary adenomas (PAs) show a broad clinicomorphological spectrum. The proliferation activity, evaluated by MIB-1 labelling index (LI), and p53 expression have been pointed as predictive markers for invasiveness and progression. The aim of this study was to evaluate the proliferation rate and p53 expression and to look for any relationships with the clinical behaviour and follow-up results in a series of Bulgarian patients with PAs. A total of 93 patients with PAs (81 hormone-secreting, 12 non-functioning), who were operated on and followed up for a period of five years, were included. The MIB-1 LI and p53 expressions were determined by immunohistochemistry and correlated with various clinical and tumour variables. The whole group of PAs showed a low proliferation rate with evident variations in a small number of cases (MIB-1 LI - 0.50 ± 0.56, from 0.1 to 3.30). MIB-1 LI correlated with tumour size (p = 0.012) and was positively related with male gender (p = 0.23) and partial surgical resection (p = 0.036). We found no significant differences regarding the age, functional activity, invasion (n = 33), expansion (n = 37) and tumour recurrences (seven cases). Only 10 cases (10.8%) showed a focal, nuclear p53 immunoreactivity. The p53 positive tumours had higher proliferation rate (p = 0.0001) but no relationship with the other clinical and tumour variables. Among all cases, there was only one case with higher MIB-1 LI (3.3%), positive p53 expression and tumour recurrence after surgery. Our results show that most PAs have a low proliferation rate and lack of p53 expression, as well as no relationship with tumour invasion or postsurgical progression.

Genome-wide gene expression profiles of thyroid carcinoma: Identification of molecular targets for treatment of thyroid carcinoma.

In order to clarify the molecular mechanism involved in thyroid carcinogenesis and to identify candidate molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 18 papillary thyroid carcinomas with a microarray representing 38,500 genes in combination with laser microbeam microdissection. We identified 243 transcripts that were commonly up-regulated and 138 transcripts that were down-regulated in thyroid carcinoma. Among these 243 transcripts identified, only 71 transcripts were reported as up-regulated genes in previous microarray studies, in which bulk cancer tissues and normal thyroid tissues were used for the analysis. We further selected genes that were overexpressed very commonly in thyroid carcinoma, though were not expressed in the normal human tissues examined. Among them, we focused on the regulator of G-protein signaling 4 (RGS4) and knocked-down its expression in thyroid cancer cells by small-interfering RNA. The effective down-regulation of its expression levels in thyroid cancer cells significantly attenuated viability of thyroid cancer cells, indicating the significant role of RGS4 in thyroid carcinogenesis. Our data should be helpful for a better understanding of the tumorigenesis of thyroid cancer and could contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with thyroid cancer.

Circulating vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours.

OBJECTIVES: The aim of the present study was to determine vascular endothelial growth factor (VEGF), prostaglandin E(2) (PGE(2)) and active renin levels in patients with hormonally active adrenal tumours. DESIGN: The study was comprised of 16 patients with primary aldosteronism, 13 patients with active Cushing's syndrome due to adrenal adenomas, 8 patients with adrenal carcinomas, 19 patients with phaeochromocytoma and 19 healthy volunteers. METHODS: Active renin in plasma was determined by a two-site immunoradiometric assay. VEGF in sera samples and PGE(2) in 24-h urine were measured by ELISA. RESULTS: VEGF was significantly elevated in all the four groups of patients as compared with the controls. VEGF levels in patients with Cushing's syndrome were higher than those in patients with primary aldosteronism. Patients with adrenal carcinomas had the highest VEGF levels and the differences reached significance as compared with patients with primary aldosteronism and phaeochromocytoma. PGE(2) levels were not significantly different among groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in patients with phaeochromocytoma compared with the controls. Active renin in patients with primary aldosteronism was significantly lower than in those with Cushing's syndrome, phaeochromocytoma and adrenal carcinoma. CONCLUSIONS: Our data indicated that the mean level of VEGF in patients with all investigated adrenal tumours was significantly higher than in healthy controls. The cortisol-producing tumours appear to have increased angiogenic potential. Angiogenesis is probably associated not only with malignancy but also with functional activity of the adrenal tumors.

Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma.

In an attempt to advance and improve the characterization of the so-called diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we studied a series of 59 thyroid carcinomas consecutively treated in a specialized center. The clinicopathologic and some of the immunohistochemical characteristics (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a multinodular or diffuse pattern of growth, and histologic features similar to those previously described in diffuse FVPTC, were compared with those of common papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of diffuse FVPTC differed significantly from common PTC and FVPTC in targeting younger patients and in exhibiting a prevalence of multicentricity, extrathyroid extension, nodal metastasis, and vascular invasion. Immunohistochemically, diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl Lewis X. No differences were observed regarding MIB 1 immunoreactivity. Regardless of the term used to designate the multicentric, invasive form of FVPTC (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of cases of FVPTC with a guarded prognosis that should be distinguished from the classic, uninodular form of FVPTC.