Rare forms of monogenic diabetes in non-European individuals. First reports of CEL and RFX6 mutations from the Indian subcontinent.

Aims: Monogenic diabetes is one of the few examples in metabolic diseases in which a real precision medicine approach can be implemented in daily clinical work. Unfortunately, most of what is known today comes from studies in Whites, thus leaving much uncertainty about the genetics and the clinical presentation of monogenic diabetes in non-Europeans. To fill this gap, we report here two pedigrees from Bangladesh with CEL- and RFX6- diabetes, two rare types of monogenic diabetes which have never been described so far in individuals of the Indian subcontinent.

Primary ciliary dyskinesia: A multicenter survey on clinical practice and patient management in Italy.

Introduction: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy.

Methods: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers.

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues.

Background/aims: Gonadotropin-releasing hormone analogues (GnRHa) represent the gold standard treatment for central precocious puberty (CPP). We aimed to assess the effects of GnRHa treatment on metabolic outcomes, bone status, and polycystic ovary syndrome (PCOS) prevalence in young girls with idiopathic CPP (ICPP).

Methods: We enrolled 94 ICPP girls who were at least 2 years after menarche and had already attained adult height at the time of the study: 56 previously treated with depot triptorelin (3.

Effect of recombinant insulin-like growth factor-1 treatment on short-term linear growth in a child with Majewski osteodysplastic primordial dwarfism type II and hepatic insufficiency.

We report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height -10.3 standard deviation score (SDS), weight -22.

Risk factors for subclinical atherosclerosis in diabetic and obese children.

Background: Increased carotid intima-media thickness (cIMT) is considered a marker of early-onset atherosclerosis and it seems to predict cardiovascular events both in obese and diabetic subjects. We aimed to evaluate early signs of atherosclerosis and investigate for predisposing factors in children and adolescents affected by type 1 diabetes (T1DM) or obesity, comparing them with healthy controls.

Methods: Out of 71 enrolled subjects (mean age 12.

Unusual pediatric co-morbility: autoimmune thyroiditis and cortico-resistant nephrotic syndrome in a 6-month-old Italian patient.

We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative.

Anti-inflammatory effects of resveratrol occur via inhibition of lipopolysaccharide-induced NF-κB activation in Caco-2 and SW480 human colon cancer cells.

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO.

Plasma membrane damage sensing and repairing. Role of heterotrimeric G-proteins and the cytoskeleton.

Different toxic agents, derived from bacteria, viruses or cells of the immune system, as well as mechanical forces generated during cell locomotion are able to open pores in the cell plasma membrane. Most of these biological agents operate through specific receptors. We studied the formation and resealing of the "non-specific" plasma membrane pores generated by the mild non-ionic detergent Triton X-100.

Organization patterns of the AGFG genes: an evolutionary study.

A number of proteins which are needed for the building of new immunodeficiency virus type 1 virions can only be translated from unspliced virus-derived pre-mRNAs. These unspliced mRNAs are shuttled through the nuclear pores reaching the cytosol when bound to the viral protein Rev. However, as a cellular co-factor Rev requires a Rev-binding protein of the AGFG family (nucleoporin-related Arf-GAP domain and FG repeats-containing proteins).

Severe hypoglycemia during successful treatment of diffuse hemangiomatosis with propranolol.

A 27-day-old male infant with diffuse hemangiomatosis of the skin and liver was treated with oral propranolol at a dosage of 2 mg/kg per day. Five months later skin and liver hemangiomas regressed almost completely. After 160 days of onset of propranolol, the patient presented with seizures on waking up.

Inflammatory responses in embryonal cardiomyocytes exposed to LPS challenge: an in vitro model of deciphering the effects of LPS on the heart.

This study is focused on the links between the major products of inflammation and cell damage induced by the administration of lipopolysaccharide (LPS) from Salmonella typhimurium in embryonal cardiomyocytes. LPS treatment for 72 hours induced transcription factor NF-kappaB activation, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression, nitric oxide (NO) and tumor necrosis factor (TNF)-alpha release. Moreover, LPS administration induced a significant cell loss, reversed by the NO-synthases inhibitor, suggesting a relationship between cell damage and iNOS-dependent NO overproduction.

Comparison between three adjuvants for a vaccine against canine leishmaniasis: In vitro evaluation of macrophage killing ability.

The aim of this study was to evaluate, in terms of dog macrophage killing ability in vitro, a vaccine based on Leishmania infantum promastigote soluble antigen (LSA) formulated with three different adjuvants (BCG, AdjuPrime, MPL/TDM/CWS). A significant increase of the macrophage killing ability was observed in dogs vaccinated with LSA+MPL/TDM/CWS after 1 month from vaccination. A similar increase of macrophage parasitocidal ability was present only after 5 months in dogs vaccinated with LSA+BCG or LSA+AdjuPrime.

Expression of UDP-glucuronosyltransferase 1A6 isoform in Caco-2 cells stimulated with lipopolysaccharide.

Glucuronidation is an important metabolic process of detoxification in all vertebrates. The reaction is catalyzed by a multigene family of UDP-glucuronosyltransferases (UGTs) able to convert many xenobiotics and endobiotics (hydrophobic substances) to inactive, water-soluble glucuronides. The UGTs play a protective role, facilitating the elimination of potentially toxic metabolites via urine, bile and feces; therefore, impairment of UGTs may have important toxicological consequences.

Differential conservation of nucleotides and conservation/mutation correlations between nucleotides, with special reference to CXC 1 and 4 and FP receptors involved in immune regulation.

Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the hydrophilic amino acids, while random mutations of the second nucleotide alter the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of the hydrophilic amino acids. In cases of a change of the hydropathic character, a second random mutation in the previously unmutated first or second nucleotide causes reversion to the original character of an additional 11 % of the originally hydrophobic-coding triplets and an additional 14 % of the originally hydrophilic-coding triplets (on average). Thus, a selection oriented towards the preservation of the hydropathic character of amino acids may be expected to eventually result in a higher conservation of the second nucleotide (as compared to the first).

Acute pancreatitis in a girl with panhypopituitarism due to craniopharyngioma on growth hormone treatment. A combination of risk factors.

Craniopharyngioma is a rare, benign, suprasellar brain tumor associated with a significant number of endocrine and metabolic impairments. Growth hormone deficiency, caused by the tumor itself or by its subsequent surgical treatment, is the most common hormone deficiency in these patients and replacement is frequently necessary. Hypothalamic obesity observed after surgery treatment, whether combined with radiotherapy or not, presents with increased abdominal fat and altered lipid profiles and is likely caused by both disruption of the mechanisms controlling satiety, hunger and energy balance and impairment of sensitivity to leptin, insulin and ghrelin axis.

Sulfonylurea treatment in a girl with neonatal diabetes (KCNJ11 R201H) and celiac disease: impact of low compliance to the gluten free diet.

A girl with celiac disease and KCNJ11 mutation was transferred to glibenclamide when 19.8 years old. When her compliance to the gluten free diet worsened, her metabolic control deteriorated.

An analysis of the human chemokine CXC receptor 4 gene.

In this article we analyze some of the structural characteristics of the coding section and the intron of the human chemokine CXC receptor 4 (a 7-transmembrane receptor) pre-mRNA. In the coding sequence the frequencies of the individual nucleotides do not depart significantly from 0.25, while in the intron the frequencies of the As and Gs are significantly lower and higher, respectively, than expected from a random distribution.

f-Met-Leu-Phe stimulates nitric oxide production in chick embryo neurons: the role of NF-kB.

N-formyl-methionyl-leucyl-phenylalanine (fMLP) is a major chemotactic factor produced by Escherichia coli and other Gram-negative bacteria. In avian models the fMLP effects and the possible expression of FPRs have been poorly investigated. This report demonstrates that fMLP stimulation in vitro is able to elicit significant cellular responses from 10-day chick embryo nerve cells.

Mutation patterns in the chemokine CXC receptor 4 gene subfamily.

Six representative CXCR4 mRNAs of fish, amphibia, birds, and mammals were selected to study the pattern of conservation/mutation of the individual nt of the coding sequences. According to an arbitrary conservation index ranging from 1 to 6, the indexes of conservation were: 5.04 for the first nt of coding triplets; 5.

Mutation, selection, and functional repair in formyl peptide receptor genes: a view on the selection processes occurring in this gene subfamily.

Formyl peptides (FPs) released by some bacteria are powerful chemoattractants and activators of granulocytes, monocytes, and macrophages, acting through the members of a subfamily of specific seven-transmembrane G-protein-coupled formyl peptide receptors (FPRs), which are expressed only in mammals. Upon stimulation, granulocytes chemotactically move towards sites of maximal FP concentration, and release different bactericidal lytic enzymes and reactive oxygen species (ROI). In some instances, such as ischemia/reperfusion, the proinflammatory mediators released by the injured tissues and the intestinal bacteria and endotoxins, which may permeate across the damaged mucosal barrier, prime the inflowing granulocytes for an enhanced ROI production, resulting in severe damage to the host tissues.

Structural relatedness between the 18S rRNA genes and the formyl peptide receptor genes: new insights into the phylogenesis of immune receptors.

In this study the authors examined the sequences of the ribosomal 18S rRNA of Drosophila and man and 16 mRNA sequences coding for different members of the family of the mammalian formyl peptide receptors (FPRs). The positions in the sequences of all >or=7-base oligonucleotide identities occurring in at least one of the 18S rRNAs and one of the FPR mRNAs were recorded. On the basis of the positional data, the Drosophila 18S-FPR and human 18S-FPR distances (in nucleotides) were determined for each identity.